Author: Suzanne Broussard, PhD
The unique characteristics and manufacturing processes of therapeutic biological products and drug compounds lays the framework for the differences in regulatory requirements for getting into the marketplace. While, biologics and drugs are both used for the same purposes — to treat, prevent, and cure diseases — biological products are much more complex in nature. By comparison, common drug compounds are relatively simple.
What exactly is a biological product?
Biological products are comprised of large and complex protein structures that are primarily derived from living material, including human, animal, and microorganisms. Proteins are often post-transcriptional modified, including glycosylation, oxidation, deamidation, and this has a profound effect on protein properties. As seen in the figure below, this contrast with conventional drug compounds, such as aspirin, that have a smaller molecular weight and are chemically synthesized. Peptides can fall into either regulatory category and are comprised of amino acids just like a protein, but peptides are smaller.
The vast differences in complexity and size are depicted in this figure.
Defining biological products and drug compounds is the first step to understanding the common and unique regulatory requirements for each. FDA’s definition is the only one that matters for the purpose of obtaining marketing approval in the United States, and the definition for biologics is in a transition period.
Hang in there while we get to the precise definitions as we transverse the regulatory pathways described in the next section.
| Acronym | Full Name |
| BLA | Biologic License Application |
| BPCI | Biologics Price Competition and Innovation Act of 2009 |
| CBER | Center for Biologics Evaluation and Research |
| CDER | Center for Drug Evaluation and Research |
| FD&C Act | Federal Food, Drug, and Cosmetic Act |
| NDA | New Drug Application |
| PHS Act | Public Health Service Act |
Click here to request for a quote for IND and BLA submission support.
The FDA Has Separate Agencies with Oversight for Biologics and Drugs.
CBER and CDER
To deal with products of dramatically different composition and manufacturing protocols, the FDA created two independent specialized centers with premarket review and oversight responsibilities: The Center for Biologics Evaluation and Research (CBER) and The Center for Drug Evaluation and Research (CDER).
FDA defines which center a product is funneled into based on its definitions. While there has been some overlap in regulatory oversight for biologics and drugs under the current regulations, new guidelines will take precedence next year.
FD&C Act and PHS Act
Therapeutic biological products are a subset of drugs and thus regulated by the Food Drug and Cosmetic Act (FD&C Act) just like common drugs. In addition, biological products are regulated by the Public Health Service Act (PHS Act) due to their complex manufacturing processes.
Current center responsibilities are listed below flowed by the newest changes.
Drug Compounds
CDER traditionally is the only center with regulatory oversight of drug products.
Biological Products
Up until March 22nd of 2020, both CBER and CDER have regulatory responsibility for therapeutic biological products under the FD&C Act and PHS Act. CDER currently regulates the following categories of therapeutic biological products.
New Definition of Biological Product
The definition of biologics changed with the newest amendments to the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act was enacted on March 23rd, 2010, and 2020 marks the end of the 10-year transition period to allow sponsors time to make a seamless transition between the CDER and CBER regulatory agencies.
The BPCI Act amends section 351(i) of the PHS Act modifying the definition of a biological product to include a “protein (except any chemically synthesized polypeptide).
Here is the FDA’s definition of these keywords in section 351(1) of the PHS Act:
Biological Product – “…a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.”
Protein – “any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size…:”
Chemically Synthesized Polypeptide – “…the term chemically synthesized polypeptide would mean any alpha amino acid polymer that: (1) is made entirely by chemical synthesis and (2) is greater than 40 amino acids but less than 100 amino acids in size.”
Peptide – “…a polymer composed of 40 or fewer amino acids…”
BLA and NDA Applications for Marketing Approval
As we will discuss in an upcoming post, both biologics and drugs must first go through a rigorous process to determine their safety and efficacy in humans before they can be sold in interstate commerce. This involves basic research and subsequent supporting clinical trials in humans. Approval of the relevant Biological Licensing Application (BLA) or New Drug Application (NDA) is the last major hurdle to getting a biologic or drug approved for marketing in the United States.
The BLA / NDA is the formal process by which a sponsor applies to FDA asking for permission to approve a new biologic or pharmaceutical for sale and marketing in the United States (21 CFR 601.2). The application tells the products full story of development and supports its use for a specific disease condition. The IND application precedes the BLA / NDA application, and the IND is actually part of the BLA / NDA as it is the living document that is kept up to date throughout the clinical evaluation process.
A key consideration is that an NDA needs to show that the drug is “safe and effective,” while the BLA is required to ensure the licensed biological product’s “safety, purity, and potency.”
The FDA ultimately makes the decision to either “approve” or “not to approve” the product based on the product’s safety and efficacy in the population for its intended use as outlined in the application. Thus, having a highly organized and well written BLA / NDA is critical for getting a product to market. Many sponsors utilize a CRO to facilitate faster market approval.
Be aware that starting March 23rd, 2020, the BPCI Act requires that approval of all “biological products” needs to be submitted and approved through a BLA. After this date, even pending or tentatively approved 505(b)2 applications will not be approved by the FDA, at least according to the current guidance document.
Therefore, the FDA recommends sponsors that are unable to complete the NDA by the transition deadline, to start down the BLA pathway now. Failure to receive final approval by the 2020 deadline for applications in progress will likely have a significant impact on proposed protein products.
Here is FDA’s preliminary list of approved biological products that will be deemed BLAs on March 23, 2020.
For questions pertaining to Project Jurisdiction, contact the CBER Product Jurisdiction Officer directly.
For questions on how Criterion Edge can help you better understand the regulatory landscape for BLAs and NDA, contact us at info@criterionedge.com.
This white paper outlines strategies for the verification of device safety and performance as well as tips to define parameters to determine the acceptability of benefit-risk.
In this practical presentation, Criterion Edge breaks down the steps of the SLR process and takes a wholistic approach to conducting an IVDR-compliant SLR. Using case studies, the presentation illustrates the effective use of SLR-derived data to develop the Scientific Validity Report (SVR) and the Clinical Performance Report (CPR).
This white paper is a companion piece to our popular webinar where we share our insights on using the Systematic
Literature Review (SLR) to Empower Data-Driven Decisions in your Organization.
In this webinar, we share the process of systematic literature review, and discuss the tools and best practices for creating a methodologically-sound systematic literature review.
In this webinar, Dr. Sarah Chavez provides an overview of the State of the Art section, and explains how it fits into the overall process of writing a successful, IVDR-compliant Performance Evaluation Report (PER) in a reasonable time frame. A complete readiness assessment and gap analysis will help you identify critical resources, feeder documents, and expertise needed to establish that your IVD may be considered “state-of-the-art.” Ultimately, knowing what the Notified Body expects to see will help you avoid project delays and discover efficiencies in the SOA development process.
This white paper is a companion piece to our popular webinar where we break down the steps of the systematic literature review (SLR) process and take a wholistic approach to conducting an In Vitro Diagnostic Regulation (IVDR)- compliant SLR.
This white paper is a companion piece to our popular webinar where we cover the state of the art process and how it
fits into the In Vitro Diagnostic Regulation (IVDR).
Fill out this form, or contact us at info@criterionedge.com, and we would be happy to answer any of your questions as well as book you an appointment to discuss your project needs during a time that works for you.
In this discussion, we provide an overview of how to plan and coordinate change within an organization to meet upcoming EU IVDR regulatory requirements. We will be highlighting key steps involved in helping medical affairs transition to a more rigorous regulatory environments, and how to evaluate talent gaps, team leadership composition, and process challenges of your product portfolio.
This white paper is a companion piece to our popular webinar where we share some of the best approaches we have
discovered for Corporate Scientific Communication Strategies.
In this discussion, our panel of proven leaders discuss the key elements that support and propel the innovation process in the medical device, pharmaceutical, and IVD industries. We will be highlighting key areas of the process, important players in the pathway to the market, and how successful innovations spawn new innovations in new markets such as the digital health space, and more.
This white paper is a companion piece to our popular webinar that uncovers what we have learned from our experience in writing Medical Device Regulation (MDR)-compliant Clinical Evaluation Reports (CERs), and how urgently applicable some of these key learnings are in preparing a robust Performance Evaluation Report (PER).
This white paper is a companion piece to our popular webinar where we share some of the biggest issues we have discovered when starting a Clinical Evaluation Report (CER) project, and how to anticipate and avoid project delays.
This companion piece to our popular webinar discusses strategies for assessing key components of your CER like clinical data sources and risk-benefit analysis.
This white paper outlines strategies to assess your CER including state of the art, safety and performance criteria, equivalence and systematic literature review.
Have the IVDR Performance Evaluation and Post Market Surveillance requirements got you tied up in knots? Where do you start? What does the end product look like? We are joined by the VP of Regulatory, Quality, and Clinical from Nextern, a collaborative medical device company bringing unmatched core competence in medical device product design and development. Criterion Edge’s President Laurie Mitchell will lead a discussion of their experiences supporting clients through MDR and IVDR requirements.
In this practical presentation, President Laurie Mitchell will: 1) discuss how an effective scientific communication plan is an important marketing tool for an organization, and 2) present five strategies to ensure your corporate objectives are supported and maximize the real-world impact of your data. Join us to learn how this applies to your organization and how to implement these strategies into your current processes.
In this practical presentation, Criterion Edge uncovers what we have learned from our experience in writing MDR-compliant CERs, and how urgently applicable some of these key learnings are in preparing a robust Performance Evaluation Report (PER).
As we all know, the MDR has significantly increased both the quality and quantity of inputs needed to complete a CER, needing more up-front planning than the reports have in the past. Based on our experiences with clients both large and small, our President, Laurie Mitchell, shares some of the biggest issues we have discovered when starting an MDR CER project. Laurie also reveals some of the most successful strategies in addressing these issues, up-front and early.
In this second installment of our 2-part webinar series, Criterion Edge shares practical presentation to help you assess your CER through the critical lens of a writer and identify possible gaps for mitigation before prior to submission to regulatory authorities.
In this webinar, we share the process of systematic literature review, and discuss the tools and best practices for creating a methodologically-sound systematic literature review.
Watch this video to learn how Criterion Edge is different from the rest.
This infographic goes through 5 key questions to go through in order to control your budget.
Leading industry experts come together to discuss how the MDR affects data management within their respective units.
This report clarifies the modifications to the equivalence guidelines in MEDDEV 2.7/1 and Quality Management Systems (QMS) ISO 13485 standard to help develop strategies.
This gap analysis addresses key revisions to evaluator qualifications and scientific validity in the Clinical Evaluation (CE) MEDDEV guideline rev.4.
The changes to 2.7/1 rev. 4 suggest the need to submit more frequent CERs to regulatory authorities, however, strategies will be discussed for managing the increased requirements.
Every time a healthcare provider makes a notation in the medical chart, a significant and valuable piece of data has been created. This paper discusses the implications of this.
This piece discusses 10 key strategies to building an efficient regulatory writing process.
In this paper, we discuss a prominent clarification on the MEDDEV 2.7.1 rev 4, establishing the “state of the art” section.
The overwhelming turnout at the ‘How to Assess Your CER for MDR Readiness, Part 1’ prompted us to host a live Q+A session where President Laurie Mitchell exclusively answers all your questions.
President Laurie Mitchell returns to continue sharing more about the importance of the systematic literature review.
Establishing and defining state of the art for a medical device is no longer an isolated task – it supports the entire Clinical Evaluation Report (CER). Multiple sections of the MEDDEV 2.7/1 rev 4 compliant CER need to be supported by state of the art data, including safety and performance, risk management, and equivalence.
In this first installment of a 2-part webinar series, Criterion Edge will present strategies for assessing key components of your CER (or CER template) for possible misalignment with significant and applicable MDR requirements.
In this webinar, President Laurie Mitchell discusses why safety reviews are essential in the entire life cycle of product development.
Kyoko Hattori from Criterion Edge returns to discuss best practices for managing the adjudication process in-house, and Brian Kelly from AG Mednet will share how the “JUDI” platform can simplify the management of adjudication.
In this webinar, learn about CECs, familiarization with regulatory guidance, decision factors leading to use of a CEC, and much more.
This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
Read more about our privacy policy here.
Strictly Necessary Cookie should be enabled at all times so that we can save your preferences for cookie settings.
If you disable this cookie, we will not be able to save your preferences. This means that every time you visit this website you will need to enable or disable cookies again.
This website uses Google Tag Manager and Pardot's tracking features to collect information such as the number of visitors to the site, and the most popular pages. Keeping this cookie enabled helps us to improve our website.
Please enable Strictly Necessary Cookies first so that we can save your preferences!
