Regulatory & Submissions · BLA Support
BLA Submission Support — Manufacturing and Comparability
The short answer
For a biologic, the process is a substantial part of the product. We support the manufacturing content of a BLA — process description, control strategy, comparability, viral and contamination control, and validation — and prepare the site for the pre-license inspection that accompanies it.
Why this matters
- Process changes across development create comparability obligations that are difficult to satisfy retrospectively.
- Contamination control strategy is examined closely for sterile and cell-based products.
- The pre-license inspection evaluates whether the licensed process is the process being run.
Applicable regulations and standards
- 21 CFR Parts 600–610
- Biologics licensing, standards and general requirements.
- 21 CFR Parts 210/211
- cGMP applied to biological drug products.
- ICH Q5A–Q5E
- Viral safety, stability, cell substrate and comparability of biotechnological products.
- FDA Guidance — Sterile Drug Products Produced by Aseptic Processing
- Aseptic processing and contamination control expectations.
What our consultants actually do
- Author and review drug substance and drug product manufacturing sections
- Build comparability protocols and assess historical process changes
- Develop and document the contamination control strategy
- Assess process validation, media fills, cleaning and hold-time studies
- Run pre-license inspection readiness reviews with former FDA investigators
- Support manufacturing documentation for the license application and post-approval changes
Across the product lifecycle
01 / DEVELOP
Process knowledge and cell bank documentation preserved for the filing.
02 / SCALE
Scale-related changes assessed for comparability as they happen.
03 / TRANSFER
Transfer to the licensed facility documented in full.
04 / VALIDATE
Process, aseptic and cleaning validation supporting licensure.
05 / MANUFACTURE
Licensed process executed as described, with contamination control maintained.
06 / MAINTAIN
Post-approval changes managed through comparability and supplements.
Problems we are usually called about
- Comparability addressed only at the end, after several undocumented process changes
- Contamination control strategy that exists as separate documents with no unifying rationale
- Media fill program not representative of worst-case commercial operations
- Manufacturing description in the BLA more idealized than the batch record
Typical deliverables
- Drug substance and drug product manufacturing sections
- Comparability strategy and protocols
- Contamination control strategy document
- Validation and aseptic program assessment
- Pre-license inspection readiness report
Frequently asked
- When should comparability work start?
- At the first significant process change. Comparability assembled retrospectively across several changes is the single most common reason biologics programs lose time before a BLA.
- Do you support cell and gene therapy programs?
- Where the work is manufacturing quality, validation, contamination control and documentation, yes. We are candid when a program needs specialist expertise we do not have in-house.
References
More for regulatory & submissions
Technical, manufacturing and quality support for US FDA submissions — written by people who have reviewed and inspected against them.
- 510(k) SupportA 510(k) is an argument for substantial equivalence, supported by evidence your quality system has to be able to produce on demand.
- PMA SupportA PMA is reviewed alongside a pre-approval inspection of the manufacturing site, which means the manufacturing section is not paperwork — it is a description of a facility that will be examined.
- De Novo SupportA De Novo asks FDA to create a classification, which means the submission has to propose the controls that will make the device type safe and effective.
- IND SupportFor an IND, the section that most often holds up a program is CMC.
- NDA SupportBy NDA, the manufacturing story has to be complete: a justified control strategy, validated process, qualified methods and a site that can demonstrate all of it during a pre-approval inspection.
- ANDA SupportGeneric applications are decided as much on manufacturing quality and data credibility as on bioequivalence.
- IDE SupportAn IDE requires a description of how the investigational device is made and controlled, and design controls apply even though the device is not yet cleared.
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