Guest Column | April 8, 2020

Harmonious Harmonization: How To Get Quality System Alignment Right

By Allan Marinelli, Quality Validation 360 Inc.

Sand Marbles Ying Yang

The rate of change in the pharmaceutical, biopharmaceutical, vaccine, and medical device industries is dizzying. Companies are constantly undergoing mergers and acquisitions, which presents significant challenges to establishing and maintaining effective quality management systems (QMSs). Some companies mistakenly assume that because they put together a master plan prior to the purchase, the elements of the integrated QMS — equipment, processes, automation, computer systems, information technology, etc. — will operate in the same fashion as they did before the merger.

This article is the second in a two-part series explaining how to successfully harmonize disparate quality systems when two companies combine. Part 1 focused on what not to do when reconciling two quality systems, providing real-life examples — drawn from the author’s experiences — from each phase of quality management system (QMS) harmonization. Here in Part 2, we will look at case studies in which companies got it right, bringing together parallel quality systems in a way that increases the probability of success.

Note: For the purposes of this discussion, we will refer to the acquiring company as “Company A” and the acquired company as “Company B" throughout the rest of the article.

Equipment And Process Validation Phase

If Company B employees or consultants follow and adhere to Company A’s  standard operating procedures (SOPs) and requirements pertaining to the execution of equipment and process validation protocols — including to correctly write the final report to capture all static and dynamic data — this increases the likelihood of successful internal and external audits by regulatory agencies. It also enhances the probability that the facility will be licensed  quickly.

Here is an example of successful harmonization during this phase: Employees from Company B were used to executing a different set of templates for the installation/operational qualification [IOQ] protocol and process validation of bioreactor 123 compared to the mandates from Company A, which encompassed different protocol instructions and acceptance criteria, along with populating the results in a certain way within the “actual result column.” Despite this fact, the employees from Company B who survived the merger were enthusiastic, motivated, and engaged — continuously willing to listen and learn new things while keeping an open mind for variations in protocol templates, execution directions, and approaches. This led to successful post-merger audit inspections towards licensure of the facility.

IT/Automation Implementation Phase

Company A introduced many information technology (IT) tools such as cDLPM (current data lifecycle processing mapping), which involved identifying key processing steps in the form of process workflows or drawings to delineate the major processing steps from the beginning to the end of the process in question. Company B had never used such tools but instead wrote IT or automation or computer system protocols based on previous history or preexisting templates that had not been updated about 15 years.

For example, the cDLPM tool can be applied to laboratory equipment (e.g., NIR) when (1) receiving the sample in the lab, (2) analysis preparation, (3) executing analysis, (4) results, (5) review applicable changes to critical data, (6) approval of data (QC/QA), and (7) archiving the data. Each of these major processing flows were then evaluated against the doctrines of CFR part 11 (does it capture and archive data, yes or no?), etc. The focus on the principles of CFR part 11 will then further enhance development of a concise process flow.

Due to the Company B team’s willingness to participate, learn something new, and constantly be open minded toward progress, Company A only had to hold a few training sessions to train the retained employees from Company B, who showed little resistance in changing a job function they had been performing for many years.

As a result, Company B easily incorporated the concepts of CFR Part 11 and new set of SOPs while embracing the new quality paradigm that was installed by Company A.

Equipment Qualification Phase

When new or legacy equipment needs to be qualified to be in alignment with Company A’s SOPs and validation lifecycle documents, careful planning, coaching sessions, kickoff meetings, other meetings, and trainings sessions should take place prior to commencing any validation activities.

In a successful case, Company A took the necessary time to coach, train, and set meetings with Company B employees without initially demanding too many deliverables (pre- and post-approval Protocols, user requirement specifications, functional specification, requirements traceability matrix, reports, etc.) be completed. This enabled the team from Company B to successfully comprehend what needed to be completed while meeting the quality expectations from Company A. As a result, when the FDA visited the site roughly nine months later, they issued no 483s or warnings — only a few recommendations that subsequently led to the licensure of that facility to manufacture product more quickly than initially projected.

Computer System Validation Phase

When Company A bought Company B, the new computerized Kaye Validator software that just came out in 2017/18 needed to be validated. This involved IOQ and performance qualification (PQ) of both the equipment portion of the Kaye Validator and the computerized portion through either of two separate protocols or one large protocol encompassing both portions.

Company B, now representing Company A, wanted to use a wrapper or shrink-wrap approach by accepting and using the default IOQ and PQ protocols and templates that the vendor (Kaye) put together to conduct the factory acceptance testing (FAT) and software FAT(sFAT) so that Company A could conveniently perform both site acceptance testing (SAT) and IOQ/PQs efficiently.

Company A was open to accept the wrapper approach and modified its preexisting SOPs, rather than fully retraining the Company B employees. Company A allowed a learning curve to take place and decided to accept the wrapper or shrink-wrap approach, which led to improved efficiency improvements without compromising its quality paradigms.

Full approval of the new computerized Kaye Validator system was completed within a month in congruence with Company A’s QMS system. (Compare this to the situation in Part 1 of this series, where approval of the system was still not complete after an entire year.)

Initiate QMS Harmonization Efforts As Early As Possible

With respect to what was discussed regarding computer system validation, there were inevitably two QMSs running in parallel, one from Company B and one from Company A. However, unlike in Part 1 — where the companies butted heads with one another, stalling progress — in this case the two companies were aligned and congruent with each other, gaining additional momentum from their unity, rather than operating as two separate entities.

This time invested in QMS harmonization at the very beginning of the merger led to continued alignment through to the fully integrated phase, thereby reducing operational cost, approval times of protocols and other documents, the amount of training iterations needed to get the employees up to speed with the new quality paradigms, and even the number of sick days per employee compared to previous years prior to the merger.

About The Author:

Allan MarinelliAllan Marinelli acquired over 25 years of worldwide cGMP experience working in Belgium, France, South Korea, China, India, Canada, and the U.S. under FDA, EMA, SFDA, KFDA, WHO, and other regulations. Since 2011, he has been the president/CEO of Quality Validation 360 Inc., providing consulting services to the (bio)pharmaceutical, medical device (Class 3), and vaccine industries. Marinelli has published 47 peer-reviewed engineering/scientific manuscripts, including book chapters on validation, risk analysis, environmental monitoring, and cleaning validation, with the Institute of Validation Technology (IVT) and the Parenteral Drug Association (PDA). He is an associate member of the American Society for Quality (ASQ). You can contact him at and connect with him on LinkedIn.