15.01.2014 |

LOGFILE No. 32/2012 - Change Management

Principles of Change Control

Author: Michael Hiob, Ph.D., Germany

Specifications and other quality goals, boundary conditions and customer requirements undergo changes all the time. Even entire projects don’t always run according to plan either, since it rarely happens that all of the required information is available from the very beginning. Therefore, changes do not indicate mistakes or failures within an organisation, but rather they are a sign of the need and the ability of a business to adapt to change. Ideally, change means improvement. In fact, however, change is often merely intended to maintain the status quo. Nevertheless, in practice, frequent, repeated changes are disruptive and confusing; they may cause interpersonal conflicts, and sometimes even lead to legal disputes. Therefore, an effective change control system is a key component of any quality assurance system. As part of the change control, experts from all relevant fields assess the effects that current or planned changes may have on a specified state. The precautions necessary to verify and document observance of the specified state are defined here.

Changes are always planned, goal-oriented and prospective in nature. This constitutes the major distinction between changes and deviations, since deviations are largely undesirable, unplanned and have to be rectified retrospectively through an analysis of the causes and consequences of an error. Therefore, deviations should not be re-interpreted and treated as unplanned changes.

Modifications, deletions and decommissioning or extensions are typical changes that can take place in a variety of ways in areas such as:

  • Methods and/or processes in production and quality control
  • Specifications and acceptance criteria,
  • Premises and equipment
  • Documents and records
  • Suppliers and service providers
  • Storage and transport
  • Personnel and business structures
  • Hardware and software

This means that changes can relate to any field that is relevant to GMP. Change control, therefore, must be a company-wide responsibility in which all types of change that could affect quality and/or reproducibility are monitored throughout the life cycle of a product or process. The quality criteria involved are assessed and the actions defined that must be taken to implement the change. Change control can also reveal that a change should not be implemented. What change control accomplishes with all of this is that changes are implemented in conformity with legal stipulations, authorisations and internal company quality assurance requirements. A working change control system is also a prerequisite for being able to implement continuous improvement processes in an effective and timely manner.

Not all changes are relevant in the sense of being subject to change control regulation, nor are all changes critical as defined in the GMP Guide, at least not to an extent that would require subsequent action. However, it should be noted that changes that are not critical from a GMP perspective can also become subject to requirements for reporting or approval (e.g. changes in a package leaflet or in ownership of a company). There are also many GMP-critical changes (e.g. changes in manufacturing facilities or testing equipment) that do not necessarily fall under reporting requirements. Therefore, what is important is not whether changes are to be classified as “major” or “minor”, but rather that the required actions to be taken are defined and implemented at the proper time.

Changes can become necessary at any point in the product lifecycle (see Figure 1), regardless of whether this change be related to specifications, the process attributes of manufacturing and quality control or the relevant facilities.

Figure 1 Changes in the Life Cycle

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There are many different possible causes or motives for changes, such as:

  • Experiences from the developmental or transfer phases
  • Results of process monitoring or statistical process control
  • Findings from quality control or stability tests
  • Continuous improvement processes and process optimisation
  • Business economic aspects (cost reduction, delivery guarantees)
  • Strategic considerations (changing suppliers, product transfers)
  • CAPA processes (Corrective and Preventive Actions)
  • Customer requests
  • Regulations (legal changes, official requirements)

It follows that change control covers a very wide field of application (see Figure 2). Change control primarily affects approved medicinal products, but it is also indirectly related to all ingredients, processes, premises, facilities and documents associated with them.

Figure 2 Range of Application of Change Control

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The type and scope of a change control system must focus on the individual operational requirements:

  • Change control in classic GMP-relevant fields serves to maintain the validated and specified status. Validated processes and qualified facilities can be so strongly affected by changes that the medicinal products they produce no longer conform to specifications with any degree of certainty. The same is true for changes in material specifications. This could call for complete revalidation and/or requalification. In such cases, a formalised procedure is required in which the risks involved in the change are assessed, the actions necessary to maintain the validated status are specified, and the change is approved only after successful revalidation.
  • First of all, authorisation holders must ensure that changes that have to be reported or approved meet the necessary regulatory requirements. Subcontracting manufacturers with no authorisations of their own and therefore no reporting obligations must ensure that their customers, the contract givers, are informed of internal operational changes that could affect the contractor givers’ authorisation documentation. A prerequisite for this is that the contract giver be integrated into the change con-trol system of the subcontracting manufacturer. Conversely, it is often the con-tract giver - the holder of an authorisa-tion - that triggers changes at the sub-contracting manufacturer as a consequence of changes in the contract giver’s authorisation. In such cases, change control not only represents an internal company responsibility, but it can also equally impact several manufacturing plants or an entire company. This is particularly true for internationally operating corporations. Changes can impact the status of authorisations in different countries or the operating equipment at different manufacturing sites.
  • The formal requirements for change control do not apply to life cycle phases prior to routine manufacturing. The stringent reporting requirements asso-ciated with approval do not have to be met in areas where medicinal products are developed, processes optimised or clinical research is carried out. Nor do changes in equipment still in the phase preceding design qualification have to be dealt with in conformity with stipulations of the GMP Guide. Instead, they can be documented in accordance with the principles of Good Engineering Practice (GEP). Nevertheless, reproducible results are expected in these phases as well. Changes in these fields should also be evaluated and documented in accordance with a defined method. At any rate, the development of a medicinal product or process, or the qualification of a system must be completely documented during the approval procedure at the latest or during pre-approval inspection.

The cost and complexity of change control procedures correspond to the degree of risk entailed in the change. Whilst change control procedures in the life cycle phases prior to approval can be informal in nature, a formalised control system is expected after approval.

A change control system is effective when it is not only theoretical in nature, but also lived out in practice, when all staff members understand and accept it, and when it is as unbureaucratic as possible and as formal as necessary. Numerous organisational and technical measures are necessary for this and are referred to within this context as change management. Change management creates the necessary prerequisites for businesses to be able to adequately plan, execute and follow up on changes within a company. Change management necessarily influences the organisational structure, the business culture and the individual behaviour of employees. Each change that is implemented will excite reactions among individuals, groups, organisations, technological sectors and contractual partners, and will impact busi-ness resources (time, money, material). Therefore, change management must take the communications culture and the value structures into consideration.

Author:

Michael Hiob, Ph.D.
Ministry for Health of Land Schleswig-Holstein, Germany

This article is a brief excerpt from chapter 19.E “Change Management” of the GMP MANUAL.

PDF: LOGFILE-32-2012-Change_Management.pdf

 

 
 
 

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