Change control and variation management are areas where coordination between functional areas is critical to a company’s agility, profits and compliance. Yet information gaps often hinder collaboration. When a company wants to change an approved product, manufacturing process or supplier, it is a highly complex and lengthy process spanning multiple departments.
It’s a significant challenge in frequency and scale:
• Lots of changes. According to one expert, a top 20 company may evaluate more than 40,000 change requests in a single year, and approve approximately 15,000 changes that must be implemented across the organization. At some life sciences companies, a single product can have more than 200 changes a year.
• Lengthy cycle times. From initial assessment to final regulatory approval and implementation, changes can take several months, or even years, to complete.1
The change control review board (CCRB) is dependent on information from other teams such as regulatory, manufacturing and supply chain to make informed go/no go decisions on requested changes. Often, however, information from regulatory is significantly delayed because organizations lack the visibility and knowledge to reliably assess the impact of a change in other regions.
In this article, we’ll focus on how to improve the role of regulatory within the change control process so that the quality team or change control review board can make informed decisions quickly and speed submissions.
MAKING A GO/NO-GO DECISION
Assessing the implications of a change request can take several weeks or even months due to information gaps that exist across functions and locations. Regulatory can speed performance along three parts of the process: identifying impacted product licenses, determining the required variation filings, and estimating the time and resources required to secure approvals.
Assessing when and where to file a variation
As process owners evaluate the impact of a change request, they need to determine which regions would be affected and the types of filings required at each location. Countries have different variation requirements, and there is room for interpretation as to whether a filing is needed. Making the wrong judgment results in extra time, effort and cost.
Health authorities recognize the uncertainty and expense that companies face related to filing variations, and they are working on new recommendations for more clarity. The International Council for Harmonization of Technical Requirements for Pharmaceuticals in Human Use (ICH) expects to release the Technical Document for ICH Q12 for public comment in October 2017 as a step toward streamlining the way post-approval changes are managed.
A main element of the initiative will be to define “established conditions” for changes that require regulatory approval upfront, at the time of the initial licensing approval. Low risk changes will not be included as established conditions and will be documented - along with any other changes - in a company’s quality system.
ICH Q12 will also encourage manufacturers to define post-approval change management protocols (PACMPs) that describe how they will manage variations during a product’s lifecycle. While PACMPs exist in the U.S. and Europe, they have not been widely adopted. The ICH hopes to stimulate broader use - this is especially important when multiple specific changes are expected for a particular product.
Establishing consistency will speed change and instill greater confidence for regulatory bodies in the way companies handle variations. With ICH Q12, firms establish the regulatory intelligence up front to ensure they make informed decisions when filing variations.
Determining the scope of impact for variation filings
As companies consider a change, it’s challenging to assess the extent of its impact on the organization. A single ingredient or manufacturing change can affect multiple products and every license where they are marketed.
In many cases, regulatory depends on quality and supply chain information to determine which products are impacted by a change. With product registrations in the Regulatory Information Management (RIM) system, regulatory can quickly determine which products are affected by a change and where those products are licensed.
Regulatory teams must frequently contact affiliates for local licensing details. If affiliates were to maintain product licenses in an easy-to-use, shared global system, the team at headquarters could quickly run an impact assessment report across geographies. Also, headquarters could gather additional data as needed via trackable workflow tasks. This helps address one of the most common delays in the assessment process, by making it easier to gather information from affiliates and providing visibility into outstanding requests.
Evaluating the scale of a proposed change
Once regulatory knows which products and licenses are affected, they must estimate the amount of time and effort required to execute the proposed change. Compiling this information can require multiple phone calls, emails and searches through spreadsheets and mountains of paper. There is an opportunity to systematically, globally capture responses from regulatory professionals during impact assessments.
Some countries restrict sponsors to one active submission at a time. Tracking this information globally provides visibility into ongoing submissions, so expected delays can be incorporated into the broader decision-making process. It also provides a historical view into the length of time it took to make past filings in different markets.