Regulatory Environment

Pharmaceuticals are considered the most highly regulated industries worldwide. Regulatory agencies
and governance organisations around the world play a vital role in ensuring the safety, quality and
efficacy of medicines, to protect the public from possible harmful drug effects.

Regulatory bodies ensure compliance with various legal and regulatory aspects of drug development
and approval and statutory obligations. Every country has its own regulatory authority, which is
responsible for enforcing the rules and issuing the guidelines to regulate the drug development process,
licensing, registration, manufacturing, marketing and labelling of pharmaceutical products in their
region. The major regulatory bodies that pharma companies interact with are the FDA (Food and Drug
Administration) and the EMA (European Medicines Agency); however, for global approval, country-
specific approval processes must be considered.

From a pharmaceutical perspective, the goal is to discover, develop, produce and market drugs to
patients, with the aspiration to cure, vaccinate or alleviate symptoms. The solutions used are critical to
ensure high-quality data are delivered efficiently to regulatory authorities to accelerate drug approval
while remaining compliant with their country-specific requirements. This has become increasingly
challenging, as regulatory pressures mount with evolving requirements. Competition is fierce, as pharma
companies identify novel medicines to address global unmet needs in rare disease areas.
Data scientists are considered data experts of structure and analysis of clinical data submitted to
regulatory authorities. However, for data scientists, there is a limited understanding of the data
submission process amongst varying regulatory authorities unless individuals are fortunate enough to be
involved directly in a submission. In addition, regulatory authorities are piloting novel approaches that
could optimise the drug review process. How can data scientists have greater influence in this area?
How can we establish strong networks between our regulatory intelligence teams to be at the forefront
of new ways of working and drive company or industry processes forward to accelerate drug approval?

This educational section will provide clarity on the regulatory process from the data scientist’s
perspective. It is important to recognise that data scientists should not only have a thorough
understanding of the submitted data but should also be familiar with how they are consumed by our
regulatory authorities. The Regulatory Framework will aim to summarise the key infliction points with
regulators, provide an understanding of how regulatory bodies use submitted data to support drug
approval and provide intelligence on emerging approaches that could influence the way clinical trial data
is submitted in the near future.

Understanding the Drug Development and Approval Process

It is important for data scientists to have a greater understanding of the drug development process and
be able to connect that with the day-to-day activities involved in clinical trial reporting. New drugs begin
in the laboratory with scientists who identify cellular and genetic factors that play a role in specific
diseases. First, the company must conduct laboratory tests and try the drug on animals, and then people,
to make sure it works and is safe.

The drug approval process varies from one country to another. At a high level, a pharmaceutical
company seeking regulatory approval to sell a new prescription drug must complete a five-step process:
discovery/concept, preclinical research, clinical research, regulatory review and regulatory post-market
safety monitoring. After testing the drug, the company submits a New Drug Application (NDA), which
must include:

• the drug’s test results

• manufacturing information to demonstrate the company can properly manufacture the drug

• data gathered during the animal studies and human clinical trials

• the company’s proposed label for the drug, which includes uses for which it has been shown to
be effective, possible risks and how to use it

• regulators, physicians and scientists then reviewing the drug research and the labelling
information on how to use the drug. If the findings show the drug’s benefits outweigh its known
risks and that the drug can be manufactured in a way that ensures a quality product, the drug is
approved and can be marketed.

Regulatory agencies don’t test the drug itself before making a decision. The agency does, however,
inspect the facilities where the drug will be manufactured, as part of the approval process. Abbreviated
processes are followed for generic and new indications for marketed drugs.
How Regulators Review Clinical Data
For major regulators such as the FDA and EMA, the time to approval can vary depending on the type of
application. For example, drugs that offer little to no improvement over other therapies already on the
market, the standard review time can be around 10 months. However, a priority review, approximately
6 months, can be considered for drugs that offer major advances in treatments or that provide
treatment where none existed. Further to this, the FDA has an accelerated approval pathway for some
drugs used for serious and life-threatening illnesses that do not have adequate treatment available.

Understanding the high-level drug approval is one element; however, it is more important for data
scientists to understand the preparation of the regulatory dossiers and then how regulators might use
the clinical data we submit. A greater understanding of these two areas provides an opportunity for
pharmaceutical companies to prepare their data in a way to ease regulatory review. Two important
areas to understand should include:

1. data submission packages developed within our own company regulatory departments to
prepare the regulatory dossiers

2. how the regulatory authorities review the dossier to aid their review to determine the safety
and efficacy of the drug.

1 - Overview: Clinical Data Review by regulatory agencies in the EU

 2 - Overview: Clinical Data Review by the US FDA

3 - Overview: Clinical Data Review by the Japanese PMDA

4 - Pinnacle 21 Enterprise vs Community version to check CDISC compliance for regulatory submissions
Emerging approaches to accelerate drug review
Accelerated drug approval is the primary objective of a drug developer. Pharma companies have a
tendency to lag behind the technology curve in comparison to other industries such as retail and
banking, mainly because in some cases it’s unclear as to what success might look like. However, more
and more pharma companies are beginning to experiment and recognise that this could transform our
industry. Understanding emerging areas and how regulators are responding to these changes feels like
an area we should be in front of.

For example, RTORs (Real-Time Oncology Reviews) and the Assessment Aid pilot programme support
the acceleration of oncology drugs. Could this eventually move other therapeutic areas? Data derived
from sources other than traditional clinical trials, such as RWD/RWE, can be used to compliment clinical
trial data by proving insights that trials can’t. These are just some of the areas, but surely companies can
develop connections with their regulatory intelligence teams to be at the forefront of these emerging
areas to ensure companies can respond to these quickly to accelerate drug approval.

5 - R for Submissions

Recommended PHUSE Educational Material

Recommended Reading

• https://www.fda.gov/drugs/real-time-review-drug-applications-now-reality-september-20-
2018-issue

• https://www.drugs.com/fda-approval-process.html

Recommended Websites

• http://www.tarius.com/

Definitions
Abbreviated New Drug Application (ANDA): An Abbreviated New Drug Application is a document
submitted by drug companies to the FDA when seeking approval of new drugs.
The European Medicines Agency (EMA) is a decentralised agency of the European Union (EU) whose
goal is to promote and protect human and animal health. The EMA does so by the use of medications in
European countries. The EMA is the European Union’s equivalent to the US Food and Drug
Administration (FDA).

The Food and Drug Administration (FDA or USFDA) is a federal agency of the United States Department
of Health and Human Services, one of the United States federal executive departments. The FDA is
responsible for protecting and promoting public health through the control and supervision of food
safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs
(medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic
radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products.

New Drug Application (NDA): A New Drug Application is a document submitted by drug companies to
the FDA when seeking approval of new drugs.

Investigational New Drug (IND): An Investigational New Drug is a drug developed by a pharmaceutical
company that is ready for clinical human trials.

Real-World Data (RWD): Data relating to patient health status routinely collected from a variety of
sources, e.g. electronic health records, medical claims billing data and data from wearables.

Real-World Evidence: (RWE): Clinical evidence about the potential benefits/risks of medical products
derived from RWD.