Recently, our colleague Marcus Delatte offered his insights about how a nonclinical expert1 can support the product development process and further advise sponsors on their applications for drug and marketing authorization approvals.

The role of the Chemistry, Manufacturing, and Controls (CMC) expert is no less important. CMC applies to the entire drug product development lifecycle, beginning during drug candidate selection and continuing through post-approval and beyond. It defines not only the manufacturing process itself, but also the quality control release testing, specifications, and stability of the product together with the manufacturing facility and all its support utilities. CMC is the connection between the drug used in clinical studies and the drug that is marketed commercially and made available to consumers. It must be adapted to the specific platform and delivery system of the drug – injectable, controlled release, inhalant, topical, solid dose, oral, and so on. Execution of an appropriately defined CMC product development strategy is vital to the success of your overall drug development program.

Regulatory Compliance

As regulatory requirements and expectations are continually evolving, a critical role of the CMC expert is ensuring that all CMC practices comply with the regulatory guidelines for the targeted region of your product. For example, if an FDA-approved finished drug product does not meet the manufacturing, packaging, or stability parameters detailed in the submission provided to the Agency, the marketing authorization is deemed noncompliant with manufacturing procedures. Unless the gaps in data are addressed under the scrutiny of regulatory Agencies, consequences for noncompliance with CMC regulatory requirements can include withdrawal of marketing authorization, suspension of product distribution, and/or consent decree and fines.

Recently, the FDA performed a survey on the success of IND submissions of oncology drugs. IND filings that were not successful primarily affected First in Human trials and were put on hold. Over 40% of these IND filings failed due to CMC problems and were submitted predominantly by sponsors with limited regulatory experience. Resolving the quality issues took an average of 114 days, but in some cases, more than two years2.

CMC at Allucent

The CMC experts at Allucent, comprised of industry experts and former Agency employees, specialize in pharmaceutical development, from early discovery through manufacturing, post-approval, and lifecycle management of a range of products. These include antibody-drug conjugates (ADCs), bispecific antibodies, fusion proteins, peptides, monoclonal antibodies (mAbs), recombinant proteins/enzymes, protein complexes, lentivirus/adeno-associated virus gene therapies, cell therapies, oligonucleotides, biosimilars, vaccines, other biologics including novel formats, and small molecule drugs.

Guidance throughout the development lifecycle

Our CMC team can help you accelerate time to market and navigate the entire drug development lifecycle, from concept to commercialization. Our experience also extends to a wide range of complex active pharmaceutical ingredients (APIs), including sterile APIs, generics, steroids, and controlled substances. Our knowledgeable team of formulation scientists and chemists have decades of experience guiding and accelerating the development and optimization of small and large molecule formulations for a variety of dosage forms. In addition, we evaluate and coordinate drug substance availability for nonclinical trials, clinical trials, and small-scale commercial manufacturing.

Collaboration with our colleagues

Our work goes hand-in-hand with the nonclinical experts who may support various aspects of chemical composition or packaging that could pose safety risks. In addition, our CMC experts work closely with the Allucent clinical team to support global clinical trials.

Strategic guidance and oversight

Allucent provides strategic guidance to our clients’ CMC product development plans. We author and review CMC documentation for regulatory submissions, perform gap analyses for various stages of development, advise on CMC regulatory strategy, and work to resolve complex CMC issues. We also facilitate interactions between clients and contract manufacturing organizations, including audits and identifying potential new vendors. The regulatory documents are jointly prepared with the nonclinical and clinical experts to be submitted to the respective Agency. Further, our CMC experts have participated in numerous interactions with global regulatory agencies including pre-IND and CTA meetings, pre BLA meetings, and Type C Meetings.

Needless to say, CMC is a critical building block for product quality throughout the process, from product development to marketing. The CMC discipline will continue to progress dynamically in the future as regulatory guidelines and agency recommendations also evolve. Having expert guidance at your side can help you stay current, streamline and accelerate processes, get timely answers and sound decision support, and crucially, deliver your product to patients in need more quickly.  

References

1. The Multifaceted Role of the Nonclinical Expert at the Center of Drug Development Teams (linkedin.com)

2. Manning et al (2020) An FDA analysis of clinical hold deficiencies affecting investigational new drug applications for oncology products. Regul Toxicol Pharmacol 110: 104511

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