Regulatory Compliance Initiative for Drug/Biologics/Combination Products Manufacturer

QSN assisted a drug/biologics/combination products manufacturing company with the successful completion of a regulatory compliance initiative, which significantly decreased their regulatory risk with the FDA.

Company Profile

  • Established in early the 60’s to discover and develop innovative medicines that cure human disease.
  • Therapeutic areas include: cardiovascular and metabolism, immunology, infectious diseases and vaccines, neuroscience, and oncology.
  • With many new products emerging into the market space, they are the largest healthcare company in the world.

Business Situation

The manufacturer wanted to increase compliance with regulatory requirements for combination products (FDA 21 CFR Part 4). The regulatory requirements would become effective on July 22, 2013, but had existed previously as a standard/guidance document to which manufacturers should already have been compliant with. The manufacturer did not have the resources in house to tackle this project in a timely manner.

Technical situation

The manufacturer currently marketed combination products which were expected to be compliant with FDA 21 CFR 820.30 as per FDA 21 CFR Part 4. All applicable combination products were expected to have a Design History File (DHF) and a complete Risk Management File (RMF).


QSN worked with the manufacturer to help with the development of a protocol that defined a process for remediation of existing DHFs, creation of new DHFs, and determination of the conformance of DHF documents to cGMPs for Design Control (FDA 21 CFR 820.30). The goal also was to provide instructions for assessing gaps and mitigating actions to ensure that legacy combination products comply with cGMPs for Design Control (FDA 21 CFR 820.30).

QSN was commissioned to facilitate and coordinate all project activities related to the build of the DHFs and RMFs. QSN developed a 2-1/2 year project schedule with the cooperation of the manufacturing site. Weekly meetings were arranged with a large cross-functional team, with QSN responsible for facilitating the meetings, updating project schedules, mitigating project risks, and managing team communications.

Many QSN consultants were responsible for executing the protocol, which required the following:

  • Review of DHF for required documents and retrievability
  • Determination if Design Verification, Design Validation and Process Validation are complete for legacy combination products
  • Identification of gaps in Design Inputs, Design Outputs, Design Verification & Validation utilizing a traceability matrix
  • Evaluation of Risk Management documentation against an evaluation form: Evaluation of Risk Assessment Documentation) and its linkage to the Annual Product Review (APR) to ensure Risk Management Files are current
  • Conducting of design review(s) and provision of evidence of closure of action items documented within a Device Design Review Issue Tracking Form


QSN was instrumental in execution of protocol, bringing over 50 products into compliance. The company was left with objective evidence to demonstrate compliance to FDA 21 CFR Part 820.30, as well as FDA 21 CFR Part 4.