The Truth About Biologics Product Development
What we discovered after 25 years & 120 biologics products
- What you need to know about the biologics product development process
- Could you unknowingly be transmitting infectious diseases?
- Why Good Manufacturing Practice (cGMP) regulations are not so straightforward for biologics
- Now you can have access to former FDA inspectors – before the FDA inspects you
- Why biologics GMPs are never black and white
- How to scale up to bridge therapeutic efficacy
- Why analytical tools alone are not enough
- What potency tests must always ensure about your product
- What an uncommon interdisciplinary approach can do for you
- How to determine if benefits of your product outweigh the risks of an immune response
Exactly what you need to know about the biologics product development process
The biologics product development process is complicated and extremely risky – to put it mildly. This is because there are scientific, regulatory, and manufacturing challenges not seen in traditional chemical drugs.
These challenging products include:
- Cellular and gene therapies
- Allergenic extracts
- Tissues and tissue products
- Blood products
- Recombinant proteins
Biologics are naturally derived from cells and tissues. They are often mixtures or complex substances. These mixtures of molecular species can be difficult to characterize as individual entities.
In some cases, the active ingredient resides in a pool of inactive substances that can affect its characteristics.
Could you unknowingly be transmitting infectious diseases?
Some biologics have the potential for transmission of infectious diseases due to the living cells in which they are manufactured.
In a sense, the manufacturing process serves to define these biologics. Quality control of the manufacturing process as well as the final product is necessary.
Poor control of the production process can lead to:
- The introduction of adventitious agents and other contaminants.
- Inadvertent changes in the properties or stability of the biologic
- These may not be detectable in final product testing.
For these reasons, the methods and reagents involved in the production process should be defined.
Why current Good Manufacturing Practice (cGMP) regulations are not so straightforward for biologics
Applying current Good Manufacturing Practice (cGMP) regulations to these living organisms is not as straightforward as with a chemical synthesis process.
Chemistry, manufacturing, and controls (CMC) sections of FDA applications should demonstrate an understanding and adherence to FDA cGMP relevant to your phase of development.
Now you can have access to former FDA inspectors – before the FDA inspects you
Our biologics consulting group of FDA experts can assist you in the application of cGMP to your biologic. The reason why our work is unique is because our people are former FDA inspectors and authors of FDA Guidelines themselves.
Whether you need help with:
- An audit of your manufacturing facility
- A mock FDA PreApproval Inspection (PAI)
- Review and resolution of FDA Form 483 observations
- Warning Letter issues
- Or writing a CMC section for your FDA submission
Our biologics consulting experts can help you.
Why biologics GMPs are never black and white
GMPs are never black and white – let us
advise you in their interpretation and application to your specific issue.
Establishing which cell characteristics are critical quality attributes (CQAs) of cell- and tissue-based biologics is crucial to gaining FDA biologics approval.
How to scale up to bridge therapeutic efficacy
These CQAs must be maintained during manufacturing process development and scale up to bridge therapeutic efficacy seen in preclinical studies. This is crucial in both early and late clinical development.
CQAs must link to the regulatory requirements for:
- and quality of these biologics.
Why analytical tools alone are not enough
A variety of analytical tools and methods are available to help you. However, selecting these methods can be challenging due to the characteristics of biologics.
Methods for the determination of identity must confirm that the product contains the intended cellular and non-cellular components. Potency testing must measure the inherent or induced biological functions(s) that is relevant to treating the intended clinical indication.
What potency tests
must always ensure about your product
Purity tests must ensure that the product does not contain undesired components, such as contaminating cell types or residual process reagents.
Biologics are sterile products; therefore, safety testing must confirm that the product does not contain microorganisms, adventitious agents, or contaminants.
Methods to test the quality of product insure that parameters, such as pH and subvisible particles, are maintained. The complex nature of biologics makes the assignment of CQAs a complicated process
What an uncommon interdisciplinary approach can do for you
Our biologics consulting approach has always been interdisciplinary, with a strong emphasis on the science underlying the product and FDA regulations.
Accordingly, our backgrounds are relevant and important for our FDA biologics consulting work.
Our backgrounds include:
- Molecular and cell biology
- Protein biochemistry
- Aseptic processing
- GCP, GLP, & GMP.
An advantage for you is that we require a minimum introduction and education of biologics in general.
How to determine if benefits of your product outweigh the risks of an immune response
Many biologics elicit immune responses. In some cases, these effects are desired (e.g., with a vaccine), but unwanted immunogenicity might be harmful.
Potential undesired effects include:
- Neutralizing or prolonging the biologic’s activity
- Forming immune complexes
- Cross-reacting with endogenous substances
The ability of a biologic to elicit an immune response must be studied in clinical trials.
We can assist you in determining if the benefits of your product outweigh the risks of an immune response by conducting an immunogenicity risk assessment.
Contact us right away to speak with an FDA biologics consulting expert
The Center for Biologics Evaluation and Research (CBER) and the Center for Drugs Evaluation and Research are the Centers within FDA that regulate biologics for human use under the Public Health Service (PHS) Act and the Federal Food, Drug and Cosmetic (FD&C) Act.
Information on CBER’s authority and areas of responsibility can be found in the article
“A PRIMER ON CBER’S REGULATORY REVIEW STRUCTURE AND PROCESS” written by Suzanne M. Sensabaugh, Biologics Consultant, HW, when she served in the FDA.
FDA regulations for biologics can be found in 21 CFR 210, 211, 312, 1270, and 600. FDA Guidelines can be found here:
With our former FDA and industry experience, we provide you with advice on regulatory, product development and cGMP for biologics. We are well positioned to assist you in gaining FDA biologics approval.
We have assisted clients from:
- United States
- China and other regions
to achieve successful outcome with the FDA
During the past 25 years, we have assisted in the development of over
120 products. Our input ranges from drafting product development plans to preparing FDA meeting packages and leading FDA meetings to writing, compiling and submission of Investigational New Drug Applications (IND) and Biologic License Applications (BLA). We provide a full spectrum of biologics consulting services. Our extensive experience and proven track record can offer you an unmatched level of industry insight.