Cleaning Limits-Why The 10-Ppm Criterion Should Be Abandoned

14:25 13/09/2023 Cleaning Limits—Why the 10-ppm Criterion should be Abandoned
Spotlight Cleaning Limits—Why the 10-ppm

Analytics Criterion should be Abandoned
Published on: January 2, 2016
Dosage Forms
Allan Ader, Andreas Flueckiger, Michel Crevoisier, David G. Dolan,
Drug Development Ester Lovsin Barle, Andrew Walsh
Pharmaceutical Technology, Pharmaceutical Technology-01-02-
Manufacturing 2016, Volume 40, Issue 1
Pages: 52–56
Outsourcing
Quality Systems
The 10-ppm criterion for the acceptable concentration of potential

Topic See All >
API in cleaning validation to minimize cross contamination into next
COVID-19 Update product has been employed for many years. This article describes
why the 10-ppm criterion, which was established based on
Analytical Method analytical limitations and estimates of acceptability, is no longer
Development necessary and why a risk-based approach should be universally
adopted.
APIs
The revised Chapter 5 of Part 1 of the European Union’s GMP
Aseptic Processing
guidelines and the European Medicines Agency’s (EMA) Guideline
Biologic Drugs on Setting Health Based Exposure Limits for Use in Risk
Identification in the Manufacture of Different Medicinal Products in
Drug Delivery
Shared Facilities came into effect in 2015 (1, 2). Both publications
Equipment expect the industry to use a “quality risk management process,

which includes a potency and toxicological evaluation” when
Excipients deciding whether to use dedicated or shared facilities to produce
pharmaceuticals. Consequently, the same comprehensive approach
Formulation
based on health risks should be followed to determine the
Packaging acceptable limits set for cleaning shared equipment. The authors
believe it is the right time to abandon the 10-ppm rule in favor of
Process Control/PAT more scientific and data-driven health based limits.
Process Development
Reasons for abandoning the 10-ppm rule
QA/QC Health authorities do not require shared equipment to be cleaned to

10 ppm of the next product. Careful reading of GMP regulatory
Regulatory Action texts (3-11), FDA’s Guide on Inspections--Cleaning Validation (12),
and the Pharmaceutical Inspection Convention and Pharmaceutical
Supply Chain
Inspection Co-operation Scheme’s (PIC/S) Recommendations on
Cleaning Validation (13) yields no indication that any of these
About Us health authorities or PIC/S ever explicitly prescribed numerical
Advertise cleaning limits. When it comes to cleaning limits, these guidelines
Contact Us all follow a similar discourse--they expect companies to abide by a
Editorial Info general duty of care, sometimes adding that the limits should be
Editorial Contacts “based on the knowledge of the materials involved.” Some of the
Editorial Advisory Board texts mention the three traditional rules originally proposed by
Do Not Sell My Personal Fourman and Mullen (14) (i.e., visually clean equipment, residue
Information levels ≤ 1/1000th daily dose, and ≤10 ppm of next product) as
Privacy Policy examples but never as binding rules. In this case, consistent with
Terms and Conditions
other performance-based regulations, the responsibility to establish
and justify cleaning limits for shared facilities remains with
pharmaceutical manufacturers.
© 2023 MJH Life Sciences™

and Pharmaceutical
Technology. All rights
reserved.
https://www.pharmtech.com/view/cleaning-limits-why-10-ppm-criterion-should-be-abandoned 1/25
Figure 1: The weight of scientific justification of the three approaches to

calculating the maximum safe surface residue (MSSR) based on the 10
ppm 1/1000 of the daily dose and permitted daily exposure (PDE)
criteria.
The 10-ppm limit goes against the basic principle of toxicology that
it is the dose that makes the poison. Parts per million (ppm) is a
concentration unit (i.e., a relative number and not an absolute one).
In chemistry parlance, it is an intensive property (such as density or
melting point) that is independent of the amount of the material,
and as such, it is not suitable to describe a dose, which is an
extensive property (such as mass or volume) that is dependent on
the amount of material. Defined as a concentration, the limit dose
will depend on the maximum amount of something else, in this
case, on the amount of the following product (or API, the
approaches vary) administered to the patient. Assuming that
therapeutic doses range from 0.1 mg to 5000 mg per day, the
amount of a contaminating substance corresponding to 10 ppm
will span the same range of 4 logs. Using a limit of 10 ppm without
risk characterization of exposure is equivalent to pretending that it
makes no difference if a drug is contaminated by 1 ng (the
equivalent of 10 ppm of 0.1 mg) or by 50 mcg (the equivalent of 10
ppm of 5000 mg) of the same substance.
Whether the contaminant is Botox or a mild antacid, the limit

amount computed by 10 ppm will be the same. Therefore,
involvement of a risk assessment scientist (e.g., toxicologist or
physician) is crucial for the characterization and differentiation of
health risks and the overall risk management process. Figure 1
compares the weight of scientific justification for three different
approaches to compute the maximum safe surface residue
(MSSR). In contrast to approaches targeting 10 ppm and 1/1000th
of the daily dose, the permitted daily exposure (PDE) approach
ensures that available preclinical and clinical data are considered in
computation of the MSSR.
Does the 10-ppm limit ensure good cleaning?

No; 10 ppm is a concentration unit that gives no indication on
cleanliness. Operationally, a sensible physical unit for cleanliness
must express the amount of residue per unit surface area (e.g.,
mg/m2). By switching from carryover (amount of residue [g]) to
cleanliness [mg/m2], the surface is normalized, and the cleanliness
of all pieces of equipment of a facility can be compared; cleaning
results between facilities and even between companies can also be
compared. When speaking of cleanliness, the size of the equipment
does not matter; “cleanliness” is an intensive property of the
equipment. Therefore, until the 10 ppm has been converted into a
cleanliness value in [mg/m2], it is not possible to say what level of
cleanliness the 10 ppm eventually represent. Depending on the
particular situation, 10 ppm may mean 1 mg/m2, which can be hard
to reach, or 50 mg/m2, which should be easy to reach.
Can 10 ppm be used to identify risks according to the EMA

guideline on shared facilities?
The EMA guideline (2) describes primarily a method for computing
health-based limits based on all available toxicological and
pharmacological information, which are termed permitted daily
exposure (PDE). The
guideline’s focus is not on how to set

cleaning limits. The PDEs are only one
element needed to set cleaning limits,
which are calculated as MSSR. The other CLICK IMAGE TO
element is the knowledge of the efficiency ENLARGE Table I
of a cleaning process, which is independent

from the next product. Therefore, while there is a link between PDEs
and cleaning limits, they are absolutely not the same. This is
expressed in the EMA guideline, which says, “these levels can be
used as a risk identification tool and can also be used to justify
carryover limits used in cleaning validation.”
An evaluation of the effect of using 10 ppm in addition to PDE to

identify risks was performed with the example of an actual product
portfolio of a multiproduct API manufacturing facility making 11
different APIs. The basic data of the APIs are given in Table I.
All changeovers from a preceding product (α) to a following product

(β) were considered. The matrix of maximum safe carryovers
(MSC) was first calculated according to Equation 1. In a second
step, the matrix of MSSR was calculated by dividing the MSC by the
equipment surface area used to make each following API (see
Equation 2).
Each cell of the MSSR matrix shown in Table II reflects an individual

product change from an API α to an API β and contains the MSSR
for the particular change (i.e., the cleanliness required to make the
corresponding API β when it is made after API α).
The PDE-based matrix in Table II shows a vivid landscape with

strong contrasts, with values from 5 to 146,970 mg/m2. It is easy to
identify the changeovers that pose the greatest risks. Comparing
the calculated MSSRs with
the results of approximately 250 swab

results that were gathered over two years,
99% of all swabs gave results <25 mg/m2;
CLICK IMAGE TO
high-risk changeovers are identified as the
ENLARGE Table II
ones that require a MSSR of < 25 mg/m2.
For example, the changeover from product D to product E was

calculated as follows:
Five products C, G, I, J, and K are potentially at risk, but only when

they follow certain products, like A, G, I, and K. Similarly A, G, I, and
K represent a risk for the other products, but not for all of them.
The comparison of the matrix of MSSR based on PDE with the

known efficiency of the cleaning processes allows for a sound
identification of risks in line with the spirit of the EMA guideline.
The comparison may give the concept of “worst-case approach to
cleaning validation” a new orientation by shifting the focus from the
hazards of worst-case products (with regard to solubility,
cleanability, toxicity, etc.) to the worst-case risks, (i.e., to the “risky”
changeovers between two products). Such risks will have to be
mitigated, for example, by development of better cleaning
procedures, avoiding high-risk changeovers by careful campaign
scheduling and dedication of certain process lines or parts of the
equipment to a group of products. It is important, however, to
accept that cleaning will have its limits: There will be cases where
the risk cannot be mitigated by cleaning alone.
How does the risk identification work with the 10-ppm rule?
Because the calculation is independent of the preceding products,
the matrix collapses to a list of batch sizes divided by 105 (see
Table III). The 10-ppm-
based MSSRs all come out in a narrow

range, between 9 and 59 mg/m2 and they CLICK IMAGE TO
do not really allow clear differentiation ENLARGE Table III
between the high- and low-risk
changeovers. Compared to PDE, the 10-
ppm calculation does not improve the detection of high risks.
In practice, the 10-ppm methodology gives the impression that

there are no low-risk changeovers. If the 10-ppm row in Table III is
followed, whenever C, D, I, or K is made, the manufacturer has to
meet the MSSR dictated by 10 ppm. The assumed cleaning limit of
25 mg/m2 will not meet the requirement to make C, D, I, or K in any
case, independently of what the preceding product was.
The high MSSR values in Table II merely reflect the low risk
associated with the corresponding changeovers. They should not
be read as cleaning limits. The suspicion that production will set
the cleaning limit at the level of the PDE-derived MSSR is not
justified. Even if the MSSR values for particular changeovers are
high, this does not justify reducing the cleaning effort, because
cleaning will still have to fulfill the requirement of visually clean
equipment. This will be sufficient to ensure a suitable minimal
hygiene standard.
The cleaning limit should also be based on the knowledge of the

capability and the reliability of the cleaning processes, and it will
ideally be set as far below the MSSR as reasonably possible.
Conclusion
There is no scientific justification for a limit concentration that
ignores the hazards presented by potential contaminants.
Implementation of the 10-ppm criterion in cleaning validation does
not ensure safe cleaning. and it may distort the identification and
analysis of cross contamination risks. Moreover, it may impose
more stringent limits for cleanliness than are required by health
authorities without adding to the patient safety. Eliminating an
unnecessary requirement serves to focus attention and resources
on high-risk situations. The 10-ppm criterion offers no scientific or
practical benefit and can be discontinued in cleaning validation
practice.
Acknowledgements
The authors would like to thank Ed Sargent and Courtney M. Callis
for their views during compilation of this manuscript.
References
1. European Commission, The Rules Governing Medicinal Products
in the European Union; Volume 4 EU Guidelines for Good
Manufacturing Practice for Medicinal Products for Human and
Veterinary Use (Brussels, August 2014).
2. EMA, Guideline on Setting Health Based Exposure Limits for Use
in Risk Identification in the Manufacture of Different Medicinal
Products in Shared Facilities (London, November 2014).
3. European Commission, Volume 4 Good Manufacturing Practice
(GMP) Guidelines, Parts I & II,
http://ec.europa.eu/health/documents/eudralex/vol-
4/index_en.htm, accessed Dec. 1, 2015.
4. European Commission, Volume 4: EU Guidelines for Good
Manufacturing Practice for Medicinal Products for Human and
Veterinary Use, Annex 15: Qualification and Validation (Brussels,
February 2014).
5. FDA, Code of Federal Regulations, Part 211 Current Good
Manufacturing Practice for Finished Pharmaceuticals,
www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cf
m?CFRPart=211, accessed Dec. 1, 2015.
6. Ministério Da Saúde Agência Nacional De Vigilância Sanitária,
Dispõe sobre as Boas Práticas de Fabricação de Insumos
Farmacêuticos Ativos (Brazil, December 2014).
7. Agência Nacional de Vigilância Sanitária--Anvisa, Validação de
limpeza para farmoquímicas,
http://portal.anvisa.gov.br/wps/wcm/connect/2443e9804f1af51ea
138bdc88f4b6a31/Guia+de+valida%C3%A7%C3%A3o+de+limpeza
+para+Farmoqu%C3%ADmicas.pdf?MOD=AJPERES, accessed Dec.
1, 2015.
8. Health Canada, Cleaning Validation Guidelines, Guide-0028
(Ontario, January 2008).
9. South Korea, Good Manufacturing Practice for Medicinal
Products for Human Use, Enforcement Regulation of
Pharmaceutical Affairs Act [Annex 2],
http://wenku.baidu.com/view/42de6028ed630b1c59eeb53e.html,
accessed Dec. 1, 2015.
10. South Korea, Provisions for Conducting Validation for Drugs,
etc, The KFDA Notification No. 2009-173 (December 2009)
11. China FDA, Good Manufacturing Practice for Drugs (2010
Revision), http://eng.sfda.gov.cn/WS03/CL0768/65113.html,
accessed Dec. 1, 2015.
12. FDA, Validation of Cleaning Processes (7/93), Guide to
Inspections: Inspections of Cleaning Processes (7/93),
www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074922.ht
m, accessed Dec. 1, 2015.

13. PIC/S, Recommendations on Validation Master Plan,
Installation and Operational Qualification, Non-Sterile Process
Validation, Cleaning Validation; PI 006-03 (September 2007).
14. G.L. Fourman and M.V. Mullen, Pharmaceutical Technology,
April issue, 54-60 (1993).
Article DetailsPharmaceutical Technology

Vol. 40, No. 1
Pages: 52–56
Citation:
When referring to this article, please cite it as M. Crevosier,
"Cleaning Limits-Why the 10-ppm Criterion should be
Abandoned," Pharmaceutical Technology 40 (1) 2016.
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Pharmaceutical Technology-01-02-2016
Orano Med and FDA Establishes Illumina

Orbit Discovery Stabilization Establishes New
Enter Period for Center in India to
Collaboration for Updated DSCSA Expand Genomics
New Novel Compliance Capabilities
Targeted Policies
Radioligand
Therapies
Orano Med and Orbit Discovery

Enter Collaboration for New Novel
Targeted Radioligand Therapies
Published on: September 11, 2023
Jill Murphy
The agreement states that Orbit will implement its bead-based

peptide display engine to discover peptide leads specific to targets
related to specific tumors.
Orano Med and Orbit Discovery announced on Sept. 11, 2023 that
they have entered a collaboration to discover specific peptide
receptor radionuclide therapies against cancer cells and advance
the development of novel radiopharmaceuticals. According to the
press release, the agreement states that Orbit will implement its
bead-based peptide display engine to discover peptide leads
specific to targets related to specific tumors.
“We’re delighted to continue expanding our existing portfolio of

partners by collaborating with Orano Med who have a strong track
record of discovering novel radiopharmaceuticals,” Neil Butt, chief
executive officer, Orbit Discovery, said in a press release. “We’re very
proud of our proprietary screening platform at Orbit and
acknowledge its role in empowering the next wave of peptide
therapeutics.”
Radioligand therapies rely on the concept of combining the ability

of biological molecules, like peptides, to target cancer cells with the
short-range cell-killing capabilities of radioisotopes. According to
the release, the approach results in an increased cytotoxic potential
toward cancer cells while still limiting toxicity to nearby healthy
cells.
This collaboration will strengthen the capabilities of Orbit’s peptide

display engine to identify peptide candidates specific to tumor-
associated targets, and the technology enables the screening of
large peptide collections through the combination of DNA encoded
libraries and bead-based presentation, according to the press
release.
“Since the inception of Orano Med, we have recognized the value of

collaboration,” said Julien Dodet, chief executive officer, Orano Med,
in a press release. “In our strategy to develop and deliver 212Pb
Targeted Alpha Therapy for cancer patients, we’re delighted to work
with Orbit Discovery and leverage its technology and expertise in
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FDA Establishes Stabilization Period

for Updated DSCSA Compliance
Policies
Daria G. Husni
The new policy will require trading partners to supply, accept, and
manage all documentation of product and ownership of prescription
drugs electronically.
FDA announced on Aug 30, 2023, that it is

creating two compliance policy guidances
initiating a year-long stabilization period for
Text sign showing those in the pharmaceutical supply chain
Industry News. that need time to adhere to Drug Supply
Business photo text Chain Security Act (DSCSA) requirements
delivering news to for electronic drug tracing at the package
the general public or level. The policy effects trading partners,
a target public | mainly manufacturers, wholesale
Image Credit: © Artur
distributors, dispensers, and repackagers.
- stock.adobe.com
The requirements are scheduled to change
on November 27, 2023, and the
stabilization period lasts until November
27, 2024.
The DSCSA went into effect in 2013, and outlines the requirements
for the electronic tracing and identification of prescription drug
distribution in the U.S. It requires trading partners to supply, accept,
and maintain documentation on prescription drugs and their chain
of ownership in the U.S. supply chain, from manufacturer to
dispenser. The current DSCSA requirements as of September 1,
2023, will be changed on November 27, 2023. The new
requirements will include mandating that trading partners manage
documentation of product and ownership electronically (previously,
partners were permitted to do so in paper format).
The two FDA-issued guidances are Enhanced Drug Distribution

Security Requirements Under Section 582(g)(1) of the Federal Food,
Drug, and Cosmetic Act – Compliance Policies (EDDSR) and
Wholesale Distributor Verification Requirement for Saleable
Returned Drug Product and Dispenser Verification Requirements
When Investigating a Suspect or Illegitimate Product —Compliance
Policies Revision 1 (WDVRS). WDVRS Revision 1 adds a year
extension (from November 27, 2023, to November 27, 2024) to a
guidance released on October of 2020 that directs distributors to
verify product identifiers before distribution. EDDSR covers FDA’s
new compliance policies for product tracing at the interoperable,
electronic, package level; these policies will go into effect on
November 27, 2023.
FDA intends for trading partners to use the stabilization period to

“build and validate interoperable systems and processes, manage
products and data, and ensure continuity of the supply chain and
product availability to patients.” It is not intended as a justification
for delaying compliance efforts with the DSCSA.
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India to Expand Genomics
Capabilities
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Illumina’s new solutions center in Bengaluru, India, will expand

access to genomics in the country.
The opening of a new solutions center in Bengaluru, India, by

Illumina, a US-based company specializing in DNA sequencing and
array-based technologies, in August 2023 not only expands
Illumina’s capabilities in genomics, but also expands access to
genomics in that country.
The new center houses a fully equipped laboratory with the latest
next-generation sequencing and array technologies. It is also fully
resourced with field applications and service engineers that can
offer broad genomics capabilities. The center will also provide
training and education to increase technical expertise and access
to genomics locally.
The new center is a permanent facility on the ground in Bengaluru

for Illumina, which has spent the past 16 years working in
partnership with Premas Life Sciences, an India-based contract
research organization and provider of niche technologies in
genomics, cell biology, and biopharma. With the help of the new
solutions center, Illumina will continue collaborative work with
Premas to grow the genomics market in India, according to an Aug.
17, 2023 company press release.
"Expanding Illumina's presence in India allows the company to

collaborate and be part of a vibrant biotech ecosystem with skilled
labor, strong research and development resources, and supportive
government policies," said Gretchen Weightman, senior vice-
president, Asia Pacific, Middle East & Africa, Illumina, in the
company press release. "In our 25th anniversary year, it's a very
exciting time to be growing our physical presence in India to drive
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health, particularly in oncology and infectious disease."
Illumina’s business in India is led by Abhishek Gupta, country

manager, and, according to Weightman in the press release,
"Abhishek brings vast knowledge and experience to Illumina India,
and we look forward to supporting him and the team as they
collaborate with and support our customers." said Weightman.
The new solutions center also presents the opportunity to pursue

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the release.
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ten23 Expands Sterile

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Further expansions of the pharmaceutical development and

manufacturing services of ten23 are happening at the BASE and
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ten23 health, a contract development and manufacturing

organization (CDMO), announced a capacity expansion for the
manufacture of sterile drug product at its Visp facility, according to
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expansion will head to VIVA 1, Visp Valais, Switzerland, at a sterile
manufacturing facility. Following successful completion of the GMP
inspection by Swissmedic and an obtained GMP license, the new
storage areas are set to become operational in September 2023.
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According to the press release, further expansions of the

pharmaceutical development and manufacturing services of ten23
are happening at the BASE and VIVA facilities to continue to
support complex sterile product development, testing, and
manufacturing. Two additional filling lines for sterile commercial
supplies of ready-to-use syringes, cartridges, and vials and liquid or
freeze-dried clinical and commercial vial supplies will all be a part
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manufacturing capacity for sophisticated and highly precise Drug
Product-presentations such as syringes and cartridges, increased
capacity until the two new production lines becoming fully
operational.” said Professor Hanns-Christian Mahler, PhD, CEO of
ten23 health, in a press release. “With recent demand increases for
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Dealing with Data: How to Keep It

Manageable
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In the Lab eNewsletter,
Advanced analytical tools generate more data in today’s labs than

ever before.
In today’s biologics/contract research organization (CRO) labs,

more data than ever are being generated on protein
characterization, thanks to advanced and more thorough analytical
technologies. Managing these volumes of data, especially in the
clinical phases of drug development, has become a real challenge
for researchers.
Clinical trial data are at the heart of how biopharma companies

develop new therapeutics for commercial launch, but developing a
new drug and bringing it to market can take a decade or more and
cost upwards of a billion dollars (1). Outsourcing clinical trial
services has become a common practice to save a biopharma
company on cost and time, but the practice brings up risks in data
transfer as well as data management.
Laboratory issues can result in a delay of data receipt as well as

poor quality of data, which can lead to rejection or rework. Data
entry issues, delays in responses to data queries, errors during data
transfer and merger, and discrepancies due to poor database setup
can all also be the cause of delays (1).
A discussion with David Hardy, PhD, senior manager, Data Analytics

and AI Enablement, Digital Science Solutions, Thermo Fisher
Scientific, explores best practices for how to approach data
management in today’s biopharmaceutical lab and highlights some
effective strategies for distilling meaningful interpretation from
these data.
Handling the data flow

BioPharm: Although solutions such as laboratory information
management systems (LIMS) and the electronic lab notebook
(ELN) have helped to address the vast amounts of data being
generated in biologics/CRO labs, what are the biggest challenges
facing LIMS and ELN?
Hardy (Thermo Fisher Scientific): The biggest challenge when it

comes to LIMS and ELNs is ensuring that these systems fit
seamlessly into laboratory processes to make sure they are used
throughout an organization, at which point they can be better used
to unlock deeper data-driven insights. Usability can also be a
challenge of many LIMS and ELN solutions, but it is critical for
company-wide, successful adoption.
Another important challenge is that, while LIMS and ELN can help
ensure data quality after data capture, they can do little to rectify
errors made through poor quality input data. To help improve data
quality at the point of data generation, labs should seek to use
automation wherever possible.
BioPharm: Do automation and digitalization truly offer solutions

that allow scientists to analyze these data in a meaningful way, or
are there as much cons as there are pros to using such advanced
technologies for the data scientist?
Hardy (Thermo Fisher Scientific): The pros and cons of using

automation and digitalization tools to analyze large amounts of
data are the same across all applications, including biologics. For
example, biologics labs still need to conduct initial validation of
their tools and constantly check them, requiring close collaboration
between the laboratory and data scientists. However, over time, the
pros of advanced digitalization and automation tools—greater
accuracy, reproducibility, efficiency, and deeper insight—vastly
outweigh any initial cons.
Importantly, even with advanced technologies, scientists face the

hurdle of understanding their data and which data fields to use.
Then, they need to be clear on which model best suits the problem
they’re trying to solve. This isn’t always easy but analytics solutions
are striving to make this simpler.
Employing good habits

BioPharm: How has the user (i.e., the scientists) experience been
affected or changed by the amount and quality of data being
generated and the ability to manage that data?
Hardy (Thermo Fisher Scientific): By their nature, scientists are

data savvy. However, with the sheer amount of data that labs
generate, as well as the need to manage these data with advanced
technologies, scientists have had to become more tech savvy. For
example, most scientists have the knowledge and skills to check
and analyze their data using languages such as R, Python, and tools
such as KNIME [Konstanz Information Miner]. Given the growing
importance of these skills, they are now widely taught to
undergraduate students.
Scientists have also embraced ‘big data,’ adopting new

technologies to such an extent that big data isn’t the obstacle it
once was. Given the increasing importance of technology in
handling and processing such data, scientists now commonly work
alongside their data science, IT [information technology], and
TechOps [technical operations] colleagues to find the optimum and
most cost-effective solution, which was less common in the past.
Beyond data capture, storage, and analysis, labs increasingly need

to be able to use their data to their full potential. Accordingly, we’ve
seen scientists increasingly focus on the FAIR (findable, accessible,
interoperable, and reusable) data principles. Data [are] only truly
useful if [they meet] these requirements.
BioPharm: What would you say are some key best practice habits
or techniques that scientists can employ to managing these data?
Hardy (Thermo Fisher Scientific): Scientists can—and should—do

several things to maximize their ability to manage these data. First,
they should embrace automation, as it’s a scientist’s best friend.
With more automation, scientists get free time to focus on more
important, value-adding activities.
Scientists should also keep in mind that managing all of these data
is a team sport. Data Science, IT, and TechOps teams are there to
help, so scientists should leverage their expertise and support to
maximize their chances of overcoming data challenges.
Finally, scientists should keep up to date on the latest technologies

for managing and analyzing data—the field is advancing very
rapidly, and taking your eye off the ball, even briefly, can lead to
missed opportunities.
Finding an effective strategy

BioPharm: What are some effective strategies that scientists can
use to ensure that they are processing quality lab data and not just
noise (are there such strategies)?
Hardy (Thermo Fisher Scientific): As the saying goes, ‘garbage in,

garbage out.’ That is to say that the root of good quality data is
good input—good experiment design followed by good execution.
Scientists can achieve these in several ways.
For example, they can adopt electronic tools such as laboratory

execution systems (LES), which help by ensuring scientists follow
methods and procedures correctly. LES and LIMS can also flag
anomalous result values that fall outside a given specification
range, helping to ensure data quality.
Scientists should also look to adopt artificial intelligence (AI)

technologies, as they can greatly help in improving data quality. But
this doesn’t have to be an overwhelming task. It can help to start
with a small project and build from there. For example, a lab might
start by using an AI-based approach to identify systematic errors,
before gradually expanding its remit and functionality. It’s important
to engage the data science team early and draw on their experience
as you embark on this new and exciting journey.
Reference
1. Johnson, J.; Kanagali, V.; Prabu, D. Third Party Laboratory Data
Management: Perspective with Respect to Clinical Data
Management. Perspect Clin Res. 2014, 5 (1), 41–44. DOI:
10.4103/2229-3485.124573
Related Content:
Analytics | Analytical Method Development | Quality Systems |
Quality Assurance/Quality Control | Development | Best Practices
In Equal The Future is the Knowledge as the

Measures: The Present: Artificial Currency of
Importance of Intelligence in Managing Risk: A
Excipient Quality Pharmaceutical Smart Investment
Manufacturing for Patients
Drug Solutions Podcast: Breaking

Through the Barriers of Drug
Development
Jill Murphy
Drug Solutions Podcast
Breaking Through the Barriers of Drug Development
Privacy policy
In this episode of the Drug Solutions podcast, Jill Murphy, Editor,

speaks with Dr. Graziella Piras, senior director of Strategic
Marketing at 908 Devices, about drug development, specifically
related to monitoring bioprocess parameters and other important
technologies important to moving the process forward.
About the speaker
Graziella has over 15 years of experience in developing products,

applications, and solutions for upstream bioprocessing. Before
joining 908 Devices, she held various positions in marketing and
R&D at Thermo Fisher Scientific, leading projects to support the Cell
Culture and Cell Therapy business.
Graziella obtained her Ph.D. in Biochemistry & Molecular Biology in

Belgium. She did her postdoc studying the role of epigenetic
regulation on cancer and development at the National Cancer
Institutes in Maryland.
About the Drug Solutions Podcast

Pharmaceutical Technology presents the Drug Solutions podcast,
where the editors will chat with industry experts from across the
pharmaceutical and biopharmaceutical supply chain. Join us as
experts share insights into your biggest questions—from the
technologies, to strategies, to regulations related to the
development and manufacture of drug products.
Listen to this podcast on SoundCloud, Spotify, Google Podcasts,

or Apple Podcasts.
Related Content:
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Therapies
The Future is the Knowledge as the Formulating with

Present: Artificial Currency of Coprocessed
Intelligence in Managing Risk: A Excipients:

Pharmaceutical Smart Investment Current Trends
Manufacturing for Patients
In Equal Measures: The Importance

of Excipient Quality
Susan Haigney
Pharmaceutical Technology,
Excipients should be treated equally when it comes to quality

management, risk assessment, and testing.
Excipients are the ingredients of a

therapeutic that change an API into a
medicine and perform roles such as
balance scale with preservatives, diluents, buffers, binders, and
pills| Image Credit: drug release controllers. These excipients
©Alexander - work in combination with the API to ensure
Stock.adobe.com the benefit of the drug product, according
to the International Pharmaceutical
Excipient Council of the Americas (IPEC-
Americas). The high levels of excipients in drugs, compared to the
API, mean the quality of these substances are just as important as
the active ingredient. “Such excipient performance expectations as
enhancing drug bioavailability, enhancing drug stability, providing
controlled and sustained-release characteristics, enabling dosage
form processability are but a few of the crucial roles excipients
provide to ensure the drug performs as intended over its shelf life,”
says IPEC-Americas.
“Excipients used in drug products may be compendial (i.e., there is

a monograph for the excipient in a recognized pharmacopeia) or
non-compendial.For blended excipient mixtures and co-processed
excipients, unless there is a monograph for that exact blend or co-
processed mixture, they are classed as non-compendial, even if all
the components individually have pharmacopeial monographs,”
says IPEC-Americas.
Low-quality excipients may be unsafe and present risks to the

patient, including exposure to toxic substances such as benzene
and diethylene glycol.“Any low-quality ingredient or adulteration that
could compromise drug product quality, safety, or performance
could lead to undesirable consequences, such as adverse events,
lack of efficacy of the drug, hospitalizations, or at worst, death,”
stresses IPEC-Americas.
According to Subba Reddy Inta, vice president and head-Quality, Dr.

Reddy’s Laboratories, North America Generics, excipients may
interact with the API and, therefore, lower the titer or assay.
Impurities may also be generated, or the absorption, distribution,
metabolism, and excretion (ADME) may be altered.
“In comparison to APIs, the repercussions of low-quality excipients

can be equally significant. While APIs are the active components
responsible for the therapeutic effect of a drug, excipients act as
essential delivery vehicles and support structures. Substandard
excipients can adversely affect the API’s stability, safety, and
performance, rendering even a high-

quality active ingredient less effective Regulations and
or potentially harmful,” caution Aryo requirements
Nikopour, VP, Global Market-
According to
Pharmaceuticals, and Shiri Hechter,
Catherine Sheehan,
senior manager, Scientific and
Senior Director at the
Technical Services, both with Nelson
US Pharmacopeia
Labs. Nikopour and Hechter also
(USP) and Otilia Koo,
point to the business risks of poor-
Chair, USP Complex
quality excipients, such as recall of
Excipients Expert
products, legations, and damage to
Committee and
the company or brand reputation. But
Executive Director,
IPEC-Americas states the finished
BMS, ensuring the
drug may be impacted regardless of
safety of excipients is
the API.
extremely important.
Steps for ensuring quality Excipients often make

up the majority of a
Excipients are usually sourced by
drug’s composition,
either the sponsor company or the
Sheehan and Koo
contract manufacturing organization
reveal, and perform a
(CMO) from ingredient manufacturers
variety of functions
and then used in the final product.
such as maintaining
The sponsor company and the CMO
pH and stability and
are responsible for ensuring the
making the drug
quality of the final pharmaceutical
palatable via
product. So, how may a sponsor
tastemasking,
company and/or a CMO ensure that
coating, and coloring.
the excipients purchased from third-
Sheehan and Koo
party vendors are safe and best
also point to the
suited for the dosage form they are
complex supply chain
creating?
of excipients that
lacks regulatory
According to Catherine Sheehan,
oversight.
senior director at the US
Pharmacopeia (USP) and Otilia Koo
“Unlike APIs, there are
Chair, USP Complex Excipients Expert
times when the
Committee and Executive Director,
quality of excipients
BMS, excipients should be sourced
is not given the
from qualified suppliers and sponsors
necessary level of
should also evaluate those suppliers.
importance because
Additionally, sponsors should check
excipients are inactive
that the supplier has a testing
ingredients.
program in place. Sponsors should
Unfortunately, the
also know who the original
impact of this can be
manufacturer of the ingredient is if it
devastating, for
is not the supplier and an original
example, the recent
manufacturer’s certificate of analysis
deaths of reportedly
should be obtained. Furthermore,
300 children in as
each shipment of incoming raw
many as seven
materials should be tested for
countries due to
applicable standards and regulations.
diethylene glycol
(DEG) and ethylene
According to IPEC-Americas, it is
glycol (EG)
important to make sure the
contamination in
manufacturer of the excipient is
cough syrups and oral
producing the excipient under good
analgesics for
manufacturing practices (GMPs)
children,” say
appropriate for excipients with the
Sheehan and Koo.
intent of that ingredient being used in
pharmaceuticals. “Finally, for
Pharmaceutical
excipients not purchased directly
Technology® spoke
from the manufacturer or a
with Sheehan and
manufacturer authorized distributor, it
is important for sponsors to Koo to find out more

understand the full supply chain back about the regulations
to the manufacturer,” says IPEC- involved in excipient
Americas. quality. In addition,
Sheehan and Koo will
A comprehensive risk assessment
be discussing these
that begins with a questionnaire is
topics at the 2023
also imperative. “Ingredient samples
AAPS PharmSci 360
are requested and received for
event.
assessment against specification
acceptance criteria. Excipient PharmTech: What are
manufacturers whose products are the USP requirements
used for the first time should be for excipients?
audited either directly or by an
Sheehan (USP) and
accredited third party acquainted with
Koo (BMS):
pharmaceutical and excipient
Pharmacopeias
manufacturing requirements such [as]
worldwide contain
the appropriate level of GMP,”
standards and test
according to IPEC-Americas.
methods to test for
Assessment of the manufacturer’s
several excipients
standard operating procedures
required for
(SOPs), batch records, and other
determining their
procedures and documents should
quality. The USP-NF
also be performed.
[United States
Quality management Pharmacopeia–
program National Formulary]
General Notices 3.10.
In addition to GMPs, according to
Applicability of
IPEC-Americas, “Compendial
Standards requires
excipients conform to the appropriate
excipients recognized
monograph using the compendial
in USP–NF to be
methods or validated equivalents.
prepared according to
Non-compendial excipients should
recognized principles
be adequately characterized and
of GMP [good
properly vetted through a risk
manufacturing
assessment to ensure the excipient
practice] and from
meets specified quality requirements,”
ingredients complying
says IPEC-Americas.
with specifications
Key elements of a quality designed to ensure
management program, according to that the resultant
Nikopour and Hechter, include substances meet the
supplier qualification and auditing, requirements of the
quality agreements with suppliers, compendial
risk assessments, testing of raw monographs. In
materials, and change control addition, USP
management. In addition, stability contains general
testing, documentation, and quality information chapters
matrices should be performed. “By on GMP requirements
implementing a robust quality for bulk
management program encompassing pharmaceutical
the above elements, pharmaceutical excipients <1078>,
manufacturers can ensure that the Good distribution
excipients used in their products are practices for bulk
of high quality and safe for patients,” pharmaceutical
say Nikopour and Hechter. excipients <1197>,
and Significant
Testing excipient quality change guide for bulk
pharmaceutical
Received excipient materials should
excipients <1195>.
go through testing and analysis, says
Nikopour and Hechter. Samples
should be tested regularly to
determine that they meet quality USP is a member of

specifications.The US the Pharmacopeial
Pharmacopeia–National Formulary Discussion Group
(USP–NF) provides methods for (PDG) with
testing compendial excipients. representatives from
the European
To test non-compendial excipients,
Pharmacopoeia and
IPEC-Americas says that suppliers
the Japanese
should develop validation methods
Pharmacopoeia
that show that the quality and
(including the very
composition of their products are
recent addition of a
consistent from batch to batch. Inta
pilot membership for
points out that additional test
the Indian
methods may be needed based on the
Pharmacopeia as it
functional requirements of the
prepares for global
sponsor. “Sometimes the supplier
expansion), with WHO
develops the different grades of a
[World Health
material to meet the formulation
Organization] as an
development requirement,” he says.
observer, to
retrospectively
Manufacturers can use many of the
harmonize standards
analytical techniques used in
for excipients
chemical analysis for testing
monographs, general
excipients, according to IPEC-
chapters, ICH
Americas. These include infrared
[International Council
spectroscopic techniques (FTIR, NIR),
for Harmonisation]
atomic absorption (AA), inductively
Q4B chapters, and
coupled plasma (ICP), mass
biotechnology
spectrometry, X-ray crystallography,
chapters. The USP–
pH, conductance, Karl Fischer water
NF has over 500
determination, as well as the many
documentary
compendial test methods (LOD, ROI,
standards for
etc.). “In addition to chemical
excipients, including
analysis, functional performance can
high-risk for
be assessed by a variety of methods;
adulteration (e.g.,
however, functionally related
EG/DEG) excipients
characteristics (FRCs) can pose some
such as Glycerin,
challenges if not considering context
Propylene Glycol,
of use.Not all FRCs will be applicable
Maltitol Solution,
to all materials or cases,” says IPEC-
Hydrogenated Starch
Americas.
Hydrolysate, and
“When a compendial monograph does Sorbitol Solution.
not exist, excipient users should
According to General
determine if other regulations,
Notices 3.10.
compendia, or guidelines can be used
Applicability of
to characterize suitable quality,” say
Standards, standards
Nikopour and Hechter.
for excipients
According to IPEC-Americas, no recognized in the
formal regulatory process exists for USP–NF are
evaluation a novel excipient outside of expressed in the
the drug product. However, for novel excipient’s
excipients that have yet to be used in monograph,
a drug formulation, Nikopour and applicable general
Hechter suggest following IPEC chapters, and General
recommendations for safety Notices. The identity,
evaluation of a novel excipient (1). quality, and purity of
FDA also provides guidance on safety excipient standards
testing for novel excipients (2). are determined by the
official tests,
procedures and
acceptance criteria,
and other
Conclusion requirements
incorporated in the
According to IPEC-Americas, “often,
monograph, in
sponsors don’t do all they should to
applicable general
qualify an excipient. However,
chapters, or in the
because they don’t, that means they
General Notices.In
may accept low quality materials
addition, USP–NF
without knowing it ... low quality
excipient monograph
excipients may be the wrong grade of
standards have over
product (not intended for use in
320 reference
pharma), adulterated, the result of
standards to support
supply chain failures or from
the test methods
manufacturers who intentionally do
included in excipient
not follow GMPs or regulations.”
monograph
standards.
Low-quality excipients present as
much of a risk to patients as low-
PharmTech: What are
quality APIs, especially because they
the requirements for
may impact the efficacy of the API.
complex excipients
They are the support system and play
such as
a significant role in ensuring drugs are
polysorbates?
safe and work as intended. It is
imperative that both sponsor Sheehan (USP) and
companies and ingredient Koo (BMS): USP-NF
manufacturers have the appropriate excipient standards
management plan in place to perform contain standards
the vital risk assessments, testing, that include test
and methods and
verification of excipients. acceptance criteria
required for
References determining their
quality. Excipients can
1. IPEC. The International
be small molecules
Pharmaceutical Council
Excipient Safety Guide for with a very well-
Pharmaceutical Excipients defined chemical
(IPEC, 2021). structure that can be

2. FDA. Guidance for Industry, characterized well
Nonclinical Studies for the analytically. Many are
Safety Evaluation of mixture-based
Pharmaceutical Excipients products (e.g., fats
(2005). and oils). Some may
come in multiple
About the author grades that can be
natural or synthetic or
Susan Haigney is managing editor of
semisynthetic. Some
Pharmaceutical Technology®.
are more complex,
Article details like polysorbates and

some may vary in
Pharmaceutical Technology degree of
Vol. 47, No. 9 characterization.
September 2023
Pages: 12–16 Polysorbates (PS) are
considered complex
Citation excipients and are
amongst the most
When referring to this article, please
versatile surfactants
cite it as Haigney, S. In Equal
in pharmaceutical use
Measures: The Importance of
used across almost
Excipient Quality. Pharmaceutical
all routes of
Technology 2023 47 (9).
administration and
dosage forms. [These
complex excipients]
are also used as
emulsifiers,
solubilizers, and
stabilizers. Some of
the PS are well
characterized in
traditional routes of
application in terms
of their chemistry.
However, they need
additional
characterization in
some of the newer
applications, such as
when used in
therapeutic biological
drugs (e.g., in
preventing protein
aggregation and
denaturation and
stabilizing therapeutic
proteins
formulations).
One of the main

challenges with
complex excipients
such as PS is
identifying
appropriate test
methods for
analyzing their
complex composition
and setting
appropriate and
meaningful
specifications. The
composition of such
excipients can vary by
inherent variations in
the source of the raw
materials used to
manufacture the
excipient and the
manufacturing
process. Further, their
performance is highly
dependent on their
composition. Thus,
these excipients
should have
standards for not only
their identification,
and levels on
impurities, but also
their composition.
One such example is

the use of the fatty
acid composition
tests and specific
tests on fats and fixed
oil content in current
USP-NF monographs
of PS 20, 40, 60, 80.

USP is also
considering
strengthening the
quality control of PS
by adding a direct
assay testing
procedure to
determine the content
of intact PS. Another
example of a complex
polymeric type of
excipient is Lactide
and Glycolide polymer
for which a new
monograph proposal
was published in USP
Pharmacopeial Forum
and includes tests for
monomer ratio and
terminated group.
—Susan Haigney
Download Issue: Pharmaceutical Technology, September
2023
Related Content:
Quality Systems | Quality Assurance/Quality Control | Supply Chain |
Formulation | Development | Compendial Compliance | Excipients
Knowledge as the Formulating with Improving

Currency of Coprocessed Manufacturing
Managing Risk: A Excipients: Flexibility with
Smart Investment Current Trends Modules
for Patients
The Future is the Present: Artificial

Intelligence in Pharmaceutical
Manufacturing
Adam C. Fisher, PhD
Pharmaceutical Technology,
FDA is anticipating how AI may advance manufacturing and

improve supply chain security.
Hollywood has long presented artificial

intelligence (AI) as a futuristic concept far
from reality, but technology has now
Cyborg hand holding eliminated the gap between science fiction
a Medical icon and and science fact. AI is here and here to
connection 3d stay; 50% of global healthcare companies
rendering | Image plan to implement AI strategies by 2025 (1).
For pharmaceutical manufacturers, AI has
Credit: ©Production the potential to revolutionize process

Perig - design and control, and thus bring benefits
stock.adobe.com to patients and challenges to regulators.
Owing to its fictionalized past, the term AI

can mean wildly different things to different people. FDA’s Center
for Drug Evaluation and Research (CDER) describes AI rather
inclusively as “a branch of computer science, statistics, and
engineering that uses algorithms or models that exhibit behaviors
such as learning, making decisions, and making predictions” (2).
The National Academies of Sciences, Engineering, and Medicine
issued a report on innovations in pharmaceutical manufacturing
that highlighted AI’s potential role in the measurement, modeling,
and control used for pharmaceutical manufacturing (3).
AI offers potential benefits to pharmaceutical manufacturers in the

form of optimized process design and control, and smart
monitoring and maintenance, to drive continuous improvement. AI
in concert with other innovative technologies might advance
pharmaceutical quality, build more resilient supply chains, and
improve the availability of medicine for patients (4). In anticipation
of these benefits, FDA is proactively preparing for the arrival of AI
technologies in pharmaceutical manufacturing.
The AI revolution
AI is an enabler of Industry 4.0, the fourth industrial revolution
characterized by integrated, autonomous, and self-organizing
production systems (5). The Industry 4.0 paradigm brings the hope
of a well-controlled, hyper-connected, digitized ecosystem and
supply chain. The COVID-19 public health emergency seems to
have accelerated the development of Industry 4.0 technologies,
such as AI, that might respond to rapidly changing supply and
demand and reduce dependence on human intervention.
So how might manufacturers deploy AI in process design and

control?
Process and scale-up optimization. AI models employing machine

learning might use process development data to more quickly
design and identify optimal process parameters or scale-up
strategies, reducing development time and waste.
Process control. Advanced process control might allow for

dynamic control of a manufacturing process which, in combination
with real-time sensor data, might be used to develop process
controls that can precisely predict the trajectory of a process.
Pharmaceutical manufacturers are expecting to adopt advanced
process control approaches that combine AI techniques with
chemistry and physics knowledge to improve manufacturing
efficiency and output.
Process monitoring and fault detection. AI methods might be used

to better monitor equipment and detect changes from optimal
performance. AI-detected deviations might trigger maintenance
activities in a manner that minimizes process downtime.
Trend monitoring. AI methods integrated with process

performance metrics might offer better trend monitoring, even
across products or locations, and consequently allow for proactive
corrective and preventive actions to address manufacturing
discrepancies before they impact the supply chain, or worse, cause
drug shortage.
The potential use of AI to monitor quality doesn’t even end at the

process. AI might also be used to monitor a product’s quality after
manufacturing, for example, for the integrity of its packaging or
presence of particulates. A vision-based quality control system
might use AI to analyze images of packaging, labels, or glass vials
to detect deviations (6). Beyond the product itself, AI might be used
to identify cluster problems from consumer complaints and
deviation reports that might contain large volumes of unstructured
text. Though the potential applications of AI in pharmaceutical
manufacturing will continue expanding, whether a manufacturer
employs AI or not, high-quality drugs should be consistently
available to patients.
Regulating AI
CDER established a Framework for Regulatory Advanced
Manufacturing Evaluation (FRAME) initiative to prepare a regulatory
framework to support the adoption of advanced manufacturing
technologies that could benefit patients, such as AI. FDA
recognizes potential benefits, and risks, of AI throughout the drug
product lifecycle. As some manufacturers look to employ AI in their
manufacturing processes, the regulatory framework will need to
enable the timely adoption of these technologies while also keeping
patients safe. CDER recognizes the need to better understand how
this new manufacturing paradigm could impact pharmaceutical
operations and regulation. The regulatory strategies of the past
might not work as effectively in an AI-enabled Industry 4.0.
However, regulators do not develop and implement manufacturing
technologies. There is a need for the stakeholders developing these
technologies to provide FDA a better understanding of where and
how AI innovations might be used in drug manufacturing. Industry
and regulators will not be able to address the issues related to AI by
working separately; true innovation requires science-based
collaboration.
In March 2023, CDER released a discussion paper to solicit public

and stakeholder input on AI in drug manufacturing to better identify
areas of policy consideration for AI technologies (2). This
discussion paper proposed areas of consideration based on CDER’s
evaluation of the existing regulatory framework: standards for
developing and validating AI models, clarification on regulatory
oversight for AI in pharmaceutical manufacturing, maintenance of
cloud applications and continuously learning AI systems that adapt
to real-time data, and data management practices commensurate
with the volume of data generated.
FDA’s public workshop on the use of AI in drug Manufacturing on

September 26–27, 2023, in conjunction with the Product Quality
Research Institute, was designed to provide another opportunity for
stakeholders to discuss key topics with regulators, such as:
Artificial Intelligence in Process Development, Process

Monitoring, and Commercial Batch Trend Monitoring
Artificial Intelligence and the Use of Big Data and Data
Management within the Pharmaceutical Quality System
Lifecycle Approaches to Management of Artificial
Intelligence.
Discussions on topics like these will help further inform the

evaluation, development, and implementation of a regulatory
framework that considers the benefits and risks of AI.
The future and AI

Like industry, regulators can employ AI to improve processes. In
fact, FDA currently uses AI for translating documents, screening
adverse event reports, and forecasting the volume of incoming
regulatory submissions. In the future, both manufacturers and
regulators might benefit from the extensive data and analysis
provided by the expanded use of AI. International regulators have
projected using AI to detect false or misleading drug information,
scan scientific literature, identify safety signals, and respond to
public inquiries (7).
While there are potential benefits of AI, there are also risks. Access
to high-quality data is a fundamental requirement for effective AI
training or learning. AI can be particularly sensitive to the
characteristics of the data used for training, testing, and validation.
The process analytical technologies providing data to AI systems
must be accurate and representative. For learning purposes, data
must represent not only process successes but also process
failures. It will be critical to ensure that data used for AI training or
learning are fit for use based on quality, reliability, and
representativeness.
Humans, and not machines, are ultimately responsible for assuring

that high-quality drugs are available to patients. Humans must be
able to interpret the information generated by AI enough to ensure,
for example, adherence to current good manufacturing practice
requirements. Even with the best intentions, there are risks for
unintended consequences. Might some even use AI for unethical
outcomes?
Still, continued technology advancement is undeniable. There’s

already talk of an Industry 5.0 paradigm which focuses on man and
machine working together, instead of separately, and considers the
manufacturer’s impact on the workforce and environment (8). In
looking ahead, it feels only appropriate to ask the uber popular AI
chatbot, ChatGPT, how things will turn out, “Will AI improve
pharmaceutical manufacturing?” “Yes, AI has the potential to
significantly improve pharmaceutical manufacturing.”
The combined efforts of regulators, industry, and scientists can

now help to realize this potential while safeguarding against risks to
patients.
References
1. USM. Top 5 AI Use Cases in Pharma & Bio Medicine.
Usmsystems.com (accessed March 8, 2023).
2. FDA. Artificial Intelligence in Drug Manufacturing. FDA.gov.
(accessed April 25, 2023).
3. National Academies of Sciences, Engineering, and Medicine.
Innovations in Pharmaceutical Manufacturing on the Horizon:
Technical Challenges,
Regulatory Issues, and Recommendations. The National
Academies Press online, DOI:10.17226/26009 (2021).
4. Kopcha, M. Beyond ‘good’ Practices.
PharmaManufacturing.com (October 20, 2022).
5. Arden, S. et al. Industry 4.0 for Pharmaceutical Manufacturing:
Preparing for the Smart Factories of the future. Inter. J.
Pharm. online,DOI:10.1016/j.ijpharm.2021.120554 (March 29,
2021).
6. FDA. Artificial Intelligence/Machine Learning Assisted Image
Analysis for Characterizing Biotherapeutics. FDA.gov.
(accessed April 13, 2023).
7. International Coalition of Medicines Regulatory Authorities.
Horizon Scanning Assessment Report–Artificial Intelligence
(2021).
8. EC. Industry 5.0, https://research-and-
innovation.ec.europa.eu/research-area/industrial-research-
and-innovation/industry-50_en, (accessed April 13, 2023).
About the author

Adam Fisher, PhD is Director of Science Staff and Immediate Office
within the Office of Pharmaceutical Quality at the Center for Drug
Evaluation and Research at FDA.
Article details
Pharmaceutical Technology
Vol. 47, No. 9
September 2023
Pages: 32–34
Citation
When referring to this article, please cite it as Fisher, A. The Future
is the Present: Artificial Intelligence in Pharmaceutical
Manufacturing. Pharmaceutical Technology 2023 47 (9).
Download Issue: Pharmaceutical Technology, September
2023
Related Content:
Quality Systems | Regulatory/GMP Compliance | Regulatory
Authority Actions | Process Control, Automation, and PAT
Formulating with Improving Preserving

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14:25 13/09/2023 Cleaning Limits—Why the 10-ppm Criterion should be Abandoned

Spotlight Cleaning Limits—Why the 10-ppm

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Figure 1: The weight of scientific justification of the three approaches to

Whether the contaminant is Botox or a mild antacid, the limit

Does the 10-ppm limit ensure good cleaning?

Can 10 ppm be used to identify risks according to the EMA

guideline’s focus is not on how to set

element is the knowledge of the efficiency ENLARGE Table I

of a cleaning process, which is independent

An evaluation of the effect of using 10 ppm in addition to PDE to

All changeovers from a preceding product (α) to a following product

Each cell of the MSSR matrix shown in Table II reflects an individual

The PDE-based matrix in Table II shows a vivid landscape with

the results of approximately 250 swab

For example, the changeover from product D to product E was

Five products C, G, I, J, and K are potentially at risk, but only when

The comparison of the matrix of MSSR based on PDE with the

based MSSRs all come out in a narrow

In practice, the 10-ppm methodology gives the impression that

The cleaning limit should also be based on the knowledge of the

m, accessed Dec. 1, 2015.

Article DetailsPharmaceutical Technology

Orano Med and FDA Establishes Illumina

Orano Med and Orbit Discovery

The agreement states that Orbit will implement its bead-based

“We’re delighted to continue expanding our existing portfolio of

Radioligand therapies rely on the concept of combining the ability

This collaboration will strengthen the capabilities of Orbit’s peptide

“Since the inception of Orano Med, we have recognized the value of

Source: Orbit Discovery

Illumina ten23 Expands Dealing with

FDA Establishes Stabilization Period

FDA announced on Aug 30, 2023, that it is

The two FDA-issued guidances are Enhanced Drug Distribution

FDA intends for trading partners to use the stabilization period to

ten23 Expands Dealing with Drug Solutions

Illumina Establishes New Center in

Illumina’s new solutions center in Bengaluru, India, will expand

The opening of a new solutions center in Bengaluru, India, by

The new center is a permanent facility on the ground in Bengaluru

"Expanding Illumina's presence in India allows the company to

Illumina’s business in India is led by Abhishek Gupta, country

The new solutions center also presents the opportunity to pursue

Dealing with Drug Solutions In Equal

ten23 Expands Sterile

Further expansions of the pharmaceutical development and

ten23 health, a contract development and manufacturing

According to the press release, further expansions of the

“We are thrilled to offer our customers additional sterile

Drug Solutions In Equal The Future is the

Dealing with Data: How to Keep It

Advanced analytical tools generate more data in today’s labs than

In today’s biologics/contract research organization (CRO) labs,

Clinical trial data are at the heart of how biopharma companies

Laboratory issues can result in a delay of data receipt as well as

A discussion with David Hardy, PhD, senior manager, Data Analytics

Handling the data flow

Hardy (Thermo Fisher Scientific): The biggest challenge when it

BioPharm: Do automation and digitalization truly offer solutions