Change Control, You’d Better Have One!

While Change Control (CC) is applied to the entire chain of events in any pharma industry, from R&D to batch release, it is the core function of any pharmaceutical plant.

“Even when a change is made to improve product or process quality, change control is required”.

In a pharmaceutical plant, CC is the “champion” of all other processes; CC must be a centralised operation bearing no uncertainty over “whose job it is”.

Some hallmarks of CC:

• Elements of any Change Control System
• The Tree E's
• The Three Changeable Elements of any Process
• Who Owns  the CC Process
• “Validation Vs Validation”

Elements of any Change Control System:

Prescribed ;Discovered ;Required; Identified ;Captured ;Recorded; Described ;Defined; Characterised;  Evaluated ;Assessed ;Analysed; Validated ;Tested ;Verified; Justified ;Rationalised; Supported; Approved ;Authorised ; Confirmed; Notified ; Reported ;Submitted; Tracked ;Traced;  Trended; Retained ;Archived ;Filed.

The Tree E's:

• Engineer a robust system
• Educate users on the system
• Enforce system policies and procedures

The Three Changeable Elements of any Process:

• What Must be Controlled; Documents, SOP’s Methods, Protocols, Specifications, Acceptance Criteria, Artwork, etc.

 QUESTION: Do the documents conform to regulations?

• Physical Reality: Processes, Operations, Packaging, Labels, etc.

 QUESTION: Does the Physical Reality conform to the documents?

• Objective Evidence and Records: Data, Reports, etc

QUESTION: Do the records support conformance claims?

 
Who Owns the CC Process (CCP)?

The QA/QC units own the CC process, NOT the change - the Initiator is the owner of the change and starts the process; together with Regulatory Affairs they review and approve the change, but all departments take part.

The initiator” project manages” the change, generating all documentation.

Change Control relies on records which are key legal documents:

• Rule of the Thumb -   assume they will be inspected by Regulators
• Therefore
• They must be complete, accurate, and supported by objective scientific evidence.

Bottom line of CC: if there is a decision to implement a change on the manufacturing of drug X, which pills will be red instead of yellow, the Initiator contacts the CC (QA/QC): identification of all units concerned and other issues such as emergency, work stoppage, etc, and CC process map building.

Next, CC writes a stakeholder matrix ; each stakeholder must report  any  required adjustments to carry on the change process ;when the round is complete the matrix  goes back to the CC; a summary of all the estimations is written and  sent  back to the stakeholders and the owner (or Initiator) who, then, sets off all procedures to  the implementation of the change .

The “Validation Vs Validation”

• Validation serves as Ground Zero for CC

QUESTION: Is the product made after the change “equivalent" to the one made before the change? (Equivalent does not mean identical).

• There Are 6 Measures of Safety and Efficacy:
  • Identity - molecular structure of excipients
  • Strength -assay, content uniformity
  • Quality - physical, chemical, biological properties
  • Purity - impurity profile, levels, degradation
  • Potency -biological activity, bioavailability, bioequivalence
  • Stability - no change in above over time

 Drug companies lacking effective, change control are running blind in terms of production quality; CC is critical when risk and safety are concerned and it cannot be shortchanged without seriously damage the company’s bottom line.

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