Establishment of a Control Procedure in Pharma for Technical Equipment, including related Utilities, Computerized Systems, and Facilities used in the Manufacture of Pharmaceuticals
A formal change control system should be established to evaluate all changes that may affect the production and control of the intermediate or API. There should be a written procedure in place to evaluate the impact of proposed changes on other possibly affected documents and to approve them. The justification for the level of criticality (e.g. the decision if a technical change has a minor or major impact on the product) should be documented.
As a part of the evaluation process, the need to obtain approval from or to notify the change authorities and customers has to be evaluated. The need to re-qualify the equipment and eventually revalidate the process must be assessed and documented. In case there is an impact on the qualification documentation, it should be reviewed and updated (e.g. IQ, OQ, PQ). All documents should be archived as necessary to demonstrate the history of the changes that took place on the equipment.
Purpose: To guide technical change control of equipment and related utilities, computerized systems [e.g. Process (PLC) and Distribution and Control Systems (DCS)], and facilities for the manufacturing of pharmaceuticals.
Scope: To technical equipment, used in the manufacture of Pharmaceuticals for use in human drug (medicinal) products. It does not include Analytical Equipment.
Definitions
Change Control: A system to evaluate, document, approve, and implement changes to technical equipment used in the manufacture of APIs to ensure a constant qualified status of the systems concerned.
Technical Change: A technical change is a planned modification (widening, replacement, removal, addition) to qualified equipment (defined state of a piece of technical equipment).
Major impact on quality: A change expected to have an impact on product quality. Changes with an uncertain impact level should be handled as major impact changes
Minor impact on quality: A change is not expected to have an impact on product quality.
“Like to like” Change : Replacement of a piece of equipment by another with identical characteristics and function (same material of construction, size, type, etc., but not necessarily from the same manufacturer)
Emergency change: An unplanned change of a piece of equipment as a result of an emergency, which needs to be repaired immediately to maintain personal or environmental safety, or preserve the quality of the product.
Process owner: the person who has the ultimate responsibility for the system which is subject to the proposed change.
QU: Quality Unit: An organizational unit independent of production that fulfills both Quality Assurance and Quality Control responsibilities.
Technical equipment: manufacturing equipment, utilities, computerized systems [e.g. Process (PLC) and Distribution and Control Systems (DCS)], and facilities used in the manufacturing of Pharmaceuticals.
Impact of Changes on Affected Systems: Important repairs and maintenance work, such as the replacement of major parts of equipment, may affect the performance of the process and the quality of the product.
Rearrangements in manufacturing areas (for example rooms with defined environmental conditions) and/or support systems (utilities, e.g.: HVAC systems, systems for water, steam, CIP/SIP systems) may result in changes in the process and as a consequence, revalidation/requalification may be necessary.
Responsibilities
Process owner
- Responsible for technical changes and following the valid change control procedure.
- Decides about the impact of the technical change on product quality (major/minor impact). The participation of the QU in this decision should be established according to the company procedure in this matter.
- It is recommended that the process owner prepare a list of changes with minor impact on product quality (standard changes).
Quality Unit (QU)
- The involvement of the QU is required if the change is thought to have, or potentially have, a major impact on the product quality.
- The QU is responsible for the implementation and maintenance of the change control system.
- The QU has to approve the standard changes list.
Process Owner and QU: Every technical change with a major impact should be assessed at least by the Process Owner and the QU. They should decide about the measures to be taken to document the change appropriately.
Criteria for criticality : Some typical questions that can help further to decide whether technical changes are critical are given below:
If the component is to be changed-
• Can directly contact the product or product components and the change is not a “like to like” one.
• Can directly affect the product quality by normal operation or control (e.g., impurity profile, crystal form, and size, residual solvent, or stability of the API).
• Indicates and records alarm functions critical to the process.
• Is used to record, output, or archive data for batch records or labels and other GMP documentation or labels.
• Is used to demonstrate compliance with the registered process.
• Can influence the quality and performance of support systems (e.g., water, steam, HVAC, etc.).
• Is used to ensure access control to critical data or functions (user identification and authenticity).
• Is used to perform analytical investigations that are relevant for batch release.
• Is used for critical calculations (e.g., analytical data that are relevant for batch release).
• Is used for batch release.
• Is used to control batch status or shelf life.
• Is used to control the production process (recipe/ process description).
• Is used to transfer critical data (interface) to another quality-relevant system.
• Is used to give information about the quality of the product (e.g., printers for process-related data).
• Is used to ensure or record critical conditions for warehouses.
• Is used to control maintenance or calibration of critical equipment.
The change may have a major impact on product quality and should therefore be carefully assessed and reviewed before implementation.
Procedure: The procedure should always begin with a request for a change. This request should be formalized in some way, for example as a form, and be signed.
- The request triggers the question of the impact of the change on the product quality. It can be necessary to define several levels of impact on the product quality but there should be at least two categories: major and minor impact. The treatment of these two options should be different.
- There should be clear rules for the decision, whether the impact of the change on the product quality is major or minor: who decides and why the decision is taken.
- For the management of changes, an early decision is required about who should be involved. The decision should be taken by the process owner, who normally has the best knowledge of the impact of changes on the product (or at least can estimate it with a high degree of certainty). The principle of double-checking should be implemented at this point in the procedure. A signature by the technical department is first required.
- Depending on the company’s procedure, the QU can be involved as an approver (to check the decision about product quality impact) or to check periodically by self-inspection audits.
- If the owner has decided that the change will have a minor impact on the quality of the product, it can be implemented. The change should be adequately documented.
- The implementation of changes with minor impact can be achieved in a very rapid and efficient manner using checklists of standard changes. The list of these changes should have been approved by the QU.
- If the decision has been taken that the change can or will have a major impact on the quality of the product, the QU has to be involved. An adequate rationale (e.g. a risk assessment) and an appropriate action plan should accompany such a change request. This builds the basis for the approval by the QU.
- After the QU approval, the change can be implemented. If other aspects are affected by the change, for example, safety aspects, additional release activities can be needed. Where such activities have been defined, these should be fulfilled before the reuse of the equipment. Release of the equipment itself can be one of
these activities. - The start of a change control system for technical equipment should be established after the completion of qualification. This will ensure that the qualified status is maintained.
- Change control during projects need not possess the same degree of formality as it can be easier regulated and can proceed without the formal and immediate involvement of the QU. The required activities in this case are adequate documentation of the changes and a periodical adaptation of the documentation.
- The change request for emergency changes can be formalized after the replacement. Emergency cases should be properly defined by each company.
List of Abbreviations
- HVAC=heating, ventilation, air conditioning
- CIP=Cleaning in Place
- SIP= Sterilisation in Place
- SOP= Standard Operation Procedure
- API= Active Pharmaceutical Ingredient
- QU= Quality Unit
Reference: APIC (Guideline for the Establishment of a Control Procedure for Technical Equipment, including related Utilities, Computerised Systems, and Facilities used in the Manufacture of API’s Rome, September 20th., 2004)