4/9/2021 Challenges in Topical Drug Manufacturing

Spotlight Challenges in Topical Drug

COVID-19 Update Manufacturing
October 17, 2012
Analytics
Equipment and Processing Report
Dosage Forms
Equipment and Processing Report, Equipment and Processing
Drug Development Report-10-17-2012, Volume 0, Issue 0

Manufacturing

Outsourcing
Consider these tools and strategies for optimizing the
Quality Systems
manufacturing process.

An ideal topical formulation can be produced using a simple,

Topic See All >
exible process. Most topical formulations developed today,

Analytical Method however, are complex and therefore require tightly controlled
Development processing parameters. September’s Equipment and Processing
Report contained an article that described ve critical process
APIs parameters: temperature, rates of heating and cooling, mixing
methods and speeds, mixing times, and ow rates. Following are
Aseptic Processing
additional strategies to optimize the manufacturing process for
Biologic Drugs topical dosage forms.

Drug Delivery Use process-control tools

Equipment

Excipients

Formulation

Packaging
Although preserved topical products do not require the strict
Process Control/PAT process controls involved in sterile manufacturing, a well
understood and controlled process is crucial.  Emulsions, for
Process Development
example, can be di cult to process because they are inherently

QA/QC thermodynamically unstable.  The use of manufacturing vessels

with programmable logic controllers (PLCs) is one tool that can
Regulatory Action provide more reliable and accurate control of the
pressure/temperature and mixing speed and times.
Supply Chain

Add ingredients in the optimal phase and order

Generally, topical formulations comprise one or more phases. 

Emulsions, for example, primarily comprise an aqueous phase
and a hydrophobic phase. Adding ingredients in the correct
phase contributes to overall stability. For example, some
polymers, such as microcrycrystalline cellulose/sodium
carboymethylcellulose, must be dispersed and hydrated prior to
adding other ingredients.

Most ingredients have an optimal method of incorporation into a

formulation. Preservatives, such as parabens, should be added
just prior to emulsi cation to reduce time in contact with water-
soluble surfactants at elevated temperatures. Polymers (e.g.,
carbomer) and gums (e.g., xanthan) must be added slowly to
avoid formation of sh eyes and other partially hydrated,
undispersed material.  These problems can be avoided by using x
eductors (e.g., Tri-Blender and Quadro Ytron dispersers) or by
preparing a slurry of polymer or gum in a medium of low or no
solubility (e.g., glycerin or glycols for certain gums or oils for
https://www.pharmtech.com/view/challenges-topical-drug-manufacturing-0 1/5
4/9/2021 Challenges in Topical Drug Manufacturing

carbomers). These thickeners act as emulsion stabilizers to

PARTNER RESOURCES
keep oils or creams suspended in water and prevent separation. 

Case Study: How Sano
Achieved 80% Lower Resin
Costs With MCC
Success Story: How BioSMB is
Transforming mAb Capture
Infographic: Explore 5 Reasons
to Switch to Multi-Column
Chromatography
Sponsored By:
Such thickeners can be shear sensitive, however, so they must
be processed with care.
As an example, DPT Labs was tasked with manufacturing a
formulation that was a fatty-acid-based emulsion neutralized
using an amine. With the amine in the water phase upon
emulsi cation, the product immediately gained viscosity,
requiring a higher mixing speed. As the product cooled, the
formulation hit a critical temperature in which it rapidly thinned
out and began splashing out of the mixing tank. DPT
resequenced the product and added the amine post-
emulsi cation. This change maintained the quality of the
product and eliminated negative effects on the formulation and
potential danger to staff.

Protect APIs from degradation

The manufacturing process must be designed to protect APIs

from physical degradation.  Some APIs, such as retinoic acid
compounds, are sensitive to both UV light and oxygen.  These
APIs can be protected by using yellow or amber light that is free
from harmful low-wavelength UV rays and by using nitrogen,
argon, or another inert gas to purge the product of oxygen.

Identify equipment constraints

The manufacturer must be able to perform all processes using

its current equipment capabilities. The scale-up path for a 1:10
batch size from the pilot or clinical size to commercial level
must exist with similar equipment. Guidance from FDA’s Scale-
Up and Postapproval Changes Semisolids (SUPAC-SS) Working
Group provides the basis of comparison for the design and
operating principles of equipment (1).

Consider regulatory requirements

Satisfying regulatory requirements for the scale-up or transfer of

a process can be challenging. To scale up a process used for
clinical batch manufacturing or transfer a commercial process
to a new manufacturing site, the equipment must at least be of
the same materials of construction and employ the same type of
mixing, as de ned in the SUPAC-SS guidance (1).

Consider an outsourcing partner

The manufacturing process can in uence a topical product’s

stability and performance.  If a formulation is transferred to a
contract manufacturer, changes in mixing speeds, temperature
controls, and order of ingredient addition may be needed. 
Outsourcing formulation development and manufacturing to a
contract development and manufacturing organization (CDMO)
allows technology transfer, scale-up, and manufacturing to take
About Us
place at one location, which ensures project continuity.
Advertise
Contact Us Reference
Editorial Info
Editorial Contacts FDA, Guidance for Industry, Nonsterile Semisolid
Editorial Advisory Board Dosage Forms, Scale-Up and Postapproval Changes:
Do Not Sell My Personal Chemistry, Manufacturing, and Controls; In Vitro
Information Release Testing and In Vivo Bioequivalence
Privacy Policy
Documentation (Rockville, MD, May 1997). x
Terms and Conditions

https://www.pharmtech.com/view/challenges-topical-drug-manufacturing-0 2/5
4/9/2021 Challenges in Topical Drug Manufacturing

Michael Lowenborg is research and development manager at

DPT Laboratories, 3300 Research Plaza, San Antonio, TX
78235, tel. 210.531.7125, Michael.Lowenborg@dptlabs.com
© 2021 MJH Life Sciences™
and Pharmaceutical
Technology. All rights Related Content:
reserved. Formulation | Outsourcing | Manufacturing | Manufacturing
Services | Development | Manufacturing, Topical Drugs |
Manufacturing, Drug Products | Equipment and Processing
Report-10-17-2012

China Approves National J&J to Take Over

BeiGene for Horizons Centre Its Product
Commercial to Provide ATMP Manufacturing
Manufacturing and Vaccine at Emergent
at its Biologics Manufacture Facility
Facility Training

China Approves BeiGene for

Commercial Manufacturing at its
Biologics Facility
April 8, 2021
Pharmaceutical Technology Editors

The China National Medical Products Administration has given

the company the green light to begin manufacturing commercial
supply of its approved anti-PD-1 antibody, tislelizumab, at its
biologics facility in Guangzhou, China.

BeiGene, a commercial-stage biotechnology company,

announced on April 7, 2021 that the China National Medical
Products Administration has given the company the green light
to begin manufacturing commercial supply of its approved anti-
programmed cell death (PD)-1 antibody, tislelizumab, at its
biologics facility in Guangzhou, China.

The 1 million-ft.2 facility currently has 8000 Lof biologics

capacity approved for commercial supply, with 64,000 additional
liters planning to be added to the site by the end of 2022,
BeiGene said in a company press release.

“We started building this large-scale, commercial biologics

manufacturing facility in 2017 to meet our expected future
demand. Since that time, tislelizumab has been approved in
several indications in China, included in the National
Reimbursement Drug List, and licensed to Novartis in Europe,
North America, and Japan,” said Xiaobin Wu, PhD, president,
chief operating o cer, and general manager of China at
BeiGene, in the press release. “With signi cantly expanded
capacity for tislelizumab and for other biologics in our pipeline,
we are continuing our strong commitment to the quality, safety,
and compliance of our products.”

Source: BeiGene

Related Content:
Supplier News | Facility Design and Engineering | Manufacturing x
| Manufacturing Equipment, Biologics

https://www.pharmtech.com/view/challenges-topical-drug-manufacturing-0 3/5
4/9/2021 Challenges in Topical Drug Manufacturing

J&J to Take Over Reshoring and

Its Product Expanding API
Manufacturing Manufacturing
at Emergent Capabilities
Facility

Advanced
Manufacturing
Technologies
Shift Outside the
Box

National Horizons Centre to

Provide ATMP and Vaccine
Manufacture Training
April 7, 2021
Pharmaceutical Technology Editors

The UK's National Horizons Centre has been confirmed as a

National Training Centre that will deliver on-site advanced
therapies and vaccine manufacturing specific training.

The National Horizons Centre (NHC) in the United Kingdom has

been con rmed as a National Training Centre that will deliver on-
site advanced therapies and vaccine manufacturing speci c
practical and digital training.

NHC was announced as a preferred bidder in December 2020 to

become one of the initial three centers to provide hands-on
training for advanced therapy medicinal products (ATMPs) and
vaccine manufacture as part of the Advanced Therapies Skills
Training Network (ATSTN)—a UK-wide initiative. ATSTN has been
awarded funding by the Department for Business Energy and
Industrial Strategy for the delivery of training centers across the
UK that will help to develop practical skills and address the
growing need in vaccine and ATMP manufacturing.

The on-site training being offered by NHC will be focused on

good practice (GxP) manufacturing, process development, and
bioprocessing techniques. In addition to hands-on training, NHC
will also create a virtual reality (VR) training facility, which will
include four VR stations alongside a tutor demonstration station.
The VR facility will be used in conjunction with the NHC
laboratory and teaching facilities to deliver the training courses.

“The UK cell and gene industry is a great place for people to

build their future. We want to see that opportunity opened up to
everyone,” said Matthew Durdy, CEO at Cell and Gene Therapy
Catapult, in a March 31, 2021 press release. “With its cutting-
edge training facilities, the [NHC] will be an integral part of the
[ATSTN’s] unique offering to anyone in the UK who wants to
advance their career in advanced therapies.”

“With the rush to develop and deliver a COVID-19 vaccine, the

importance of the biomanufacturing and bioprocessing sectors x
has never been so apparent,” added Jen Vanderhoven, director
of NHC, in the press release. “We’ve worked very closely with
leading gures across the bioindustry sector to ensure that each
https://www.pharmtech.com/view/challenges-topical-drug-manufacturing-0 4/5
4/9/2021 Challenges in Topical Drug Manufacturing

of these courses will address the requisite technical and digital

needs. We pride ourselves on our ability to be responsive to the
sector’s needs, so we’re very pleased to have been able to react
quickly and develop these courses, which will deliver vital skills
needed for vaccine manufacturing and advanced therapies and
to grow this important industry.”

The training courses will be available at NHC from May 2021.

Courses will cover upstream and downstream bioprocessing,
analytical techniques for bioprocessing, process control and
automation, viral vector manufacturing, biologics manufacturing,
data integrity, computer systems validation and IT compliance,
good manufacturing practice for biologics, practical proteomics,
and ow cytometry for bioprocessing.

Source: CGT Catapult

Related Content:
Industry News | PharmTech Europe News | Supplier News |
Manufacturing, Gene Therapies | Manufacturing, Cell Therapies |
Manufacturing | Bio/Pharma News

Reshoring and
Expanding API
Manufacturing
Capabilities

Advanced Balancing the

Manufacturing Art and Science
Technologies of Topical Drug
Shift Outside the Formulation
Box

https://www.pharmtech.com/view/challenges-topical-drug-manufacturing-0 5/5