Maintenance Qualification: Improving Compliance and Performance in Pharmaceutical Manufacturing

This article describes an approach to maintenance management that delivers enhanced compliance for direct impact GMP systems and improved maintenance effectiveness for indirect or low impact systems.

A.D. Martin Brown is a

principal consultant and

Jim McCabe is a sector

manager at ABB Engineering Services, UK.

aintenance engineers are the unsung heroes of the pharmaceutical production process. Once the project engineers have left it is the maintenance engineers who manage and mitigate the risks associated with ongoing manufacturing operations.These include risks to product integrity due to contamination or malfunctioning equipment; risks to production through poor equipment availability; risks associated with health, safety and the environment; and inspection risks arising from an inability to demonstrate that adequate maintenance controls are in place. Yet in an environment where there is increased focus on cost of production, it is often the maintenance budget that faces cuts. Where can these cuts be

made without compromising current good manufacturing practice (cGMP) compliance? Maintenance qualification provides documentary evidence of the maintenance controls in place to maintain cGMP, and identifies the optimum maintenance policies required for cost-effective and efficient operations. The approach is a rapid methodology used to understand the risk of equipment failure to identify the critical equipment items, that is, those items that present the greatest business risk; and to identify measures to manage the risk. These measures include: maintenance policy and practices operations policy and practices fitness for purpose
PHARMACEUTICAL TECHNOLOGY EUROPE, 17(3), 2025 (2005)

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predictive maintenance technical support spares cover protective systems. By eliminating unnecessary or nonvalue-adding maintenance routines and by focussing resources on those equipment items with the greatest impact on business performance can enhance compliance and reduce maintenance costs and unplanned downtime (Figure 1).

Methodology
A key requirement of the methodology is to channel effort only on critical equipment. This is determined by assessing whether the equipment or system is GMP-critical and by further assessing the business risk of failure. The maintenance controls in place to ensure the continued compliance of GMP-critical equipment are reviewed and documented. Maintenance controls for other equipment items are assessed to identify opportunities to improve reliability and make efficiency savings (Figure 2). Prescreening. With a large number of equipment items to consider, a prescreening assessment is used to improve the overall efficiency of the process. Prescreening uses the concept of positive exclusion to identify noncritical items and, thereby, reduce the load on the subsequent criticality analysis. The assessment tests all equipment items against two criteria risk and consequence using a few (typically two) simple questions. A prescreening assessment can substantially reduce the numbers of items to be assessed during criticality analysis; in some cases by 80%. Impact assessment. Following prescreening, GMP criticality is determined by a system impact assessment.1 Systems are divided into direct, indirect or nonimpact systems, which are defined as follows: Direct impact a system that is expected to have a direct impact on product quality, via product contact or direct influence on quality. Indirect impact system a system that is not expected to have a direct impact on product quality, but typically supports a direct impact system. Nonimpact system a system

that will not have any impact, either directly or indirectly, on product quality. The impact assessment process is divided into two main activities. The first identifies the system boundaries and evaluates the impact of the system on the product quality. The second evaluates the criticality of the components within each direct impact system with respect to their role in assuring product quality. Maintenance qualification. For direct impact systems or those indirect impact systems with critical compo-

nents, maintenance qualification will document and review the adequacy of the maintenance controls in place to ensure system/component integrity. The equipment should not adversely affect the safety, identity, strength, quality or purity of the manufactured product, either through its construction or through contamination from other manufacturing operations.2 Maintaining a validated state requires a formal, documented periodic review of systems and processes. The maintenance qualification con-

Figure 1 Maintenance qualification.

Current maintenance regime Future maintenance regime

Extent and cost of maintenance

High Direct Medium Indirect Low Nonimpacting Systems

Extent and cost of maintenance

Documented procedures/processes Fully trained and enabled people

Equipment availability Maintenance costs Cost of ongoing compliance

Figure 2 The maintenance qualification and definition process.

System impact assessment Direct impact Maintenance qualification Option Noncritical Indirect impact No impact Very high Detailed FMECA High Medium Maintenance frequency optimization Spares optimization Contingency planning Maintenance policy setting High/medium Generic FMEA Low Criticality analysis Generic policy Option GMP spares

Prescreening

Option

Documented equipment maintenance strategy

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Figure 3 Failure modes.

Plant Item Number
R111_A BC122_Z1 F101_BK JC821

Plant Item Description

Assumed Failure Mode

Additional Information

Agitator Double Batching Hopper Catalyst Filter HTF Chiller

Shaft failure Blockage

Bottom shaft seal failure (lip seal) frequent & catastrophic

Spurious trip

Figure 4 Criticality criteria.

Criticality or Impact
Annual Maintenance Budget Maintenance Criticality (M) Safety (Immediate Effect) Health (long Term Effect)

3 2 2 1

1 2 1 1

3 1 2 1

9 16 12 5

5 2 1 2

4 2 2 2

20 1000 16 6 100 200

48 4 12 2

48.0 0.4 2.4 2.0

7 5 7

5 1 2

4 2 2

4 2 3 4

2 2 3 1

20 1000

15 0.5 4

cept can be dovetailed into a riskbased periodic review process. Maintenance qualification procedures automatically generate evidence that equipment and processes are under full control in line with their GMP duties and intended use. This ordered information enables the periodic review to be a check box exercise and facilitates automation of the review. Only if this high level check uncovers abnormalities or nonconformance does the periodic review progress to a more detailed level. This can lead to substantial savings in the periodic review of GMP items. The qualification process itself will be conducted in accordance with a standard operating procedure (SOP) and will address the following elements: The validation status of all relevant systems. The availability and currentness of supporting information (e.g., operating and maintenance manuals, spare parts lists, as-built drawings and equipment log books). Whether documented maintenance and calibration policies and procedures, including schedules, are established. Whether instrumentation has a valid calibration status, and if this is clearly identified and any configurable parameters are appropriate and documented. Whether equipment has, and is clearly identified as having, a valid maintenance status. Whether equipment cleaning status and content are clearly identified. Whether the maintenance and calibration records are up to date. Whether change controls are in place. Whether appropriate training programmes are in place. Documenting existing controls is a necessary, but not sufficient, part of reviewing the adequacy of preventive maintenance of equipment. The failure modes of equipment and supporting systems must be assessed to determine whether any of these situations have the potential to adversely affect the identity, strength, quality or purity of the drug (Figure 3). This approach will consider equipment failure modes,

Production Criticality (P)

Customer Criticality (C)

K/hr

hour

PHARMACEUTICAL TECHNOLOGY EUROPE, 17(3), 2025 (2005)

GMP Criticality (GMP)

Production Loss Rate

HSE Criticality (HSE)

Customer Impact

Failure Downtime

Production Loss

Environment

Repair Cost

Quality

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common failure modes within systems and failure modes of supporting business processes. For example, the use of incorrect spare parts can be a source of contamination if these are in product contact applications. Such failures can occur when GMP spares are not sufficiently controlled or when suppliers provide in good faith a similar part to replace an item that is out of stock. A vulnerability analysis reviews the management of these risks for critical systems by evaluating factors such as maintenance policy and practices, predictive maintenance and protective systems to assess the adequacy of maintenance controls. The best results are achieved by using a team of operators and maintenance personnel facilitated by an experienced moderator to provide objective guidance on failure modes, guide the discussion, and maintain pace and momentum. The maintenance controls in place can be reviewed to assess their effectiveness and any recommendations for corrective actions identified. The qualification report will summarize the results of the review, comment on any deviations observed and identify any changes necessary to correct deficiencies. Criticality analysis. Business criti-

cality analysis is applied to indirect impact and nondirect impact systems. The technique uses a range of criteria to address the areas of business risk that are considered relevant to the particular operation. A typical set is: product quality and customer criticality health, safety and environment (HSE) criticality business criticality GMP criticality. The effects of potential equipment failure modes are rated using established word models against each of the criteria enabling the overall criticality to be established (Figure 4). The criteria used to evaluate the consequences of the failures are tailored to suit the client operations; for example, what is a significant production loss or impact on maintenance costs? In addition to ranking the equipment according to criticality, the process also highlights the underlying issues. This information is recorded for subsequent use. An additional option for our criticality assessor is to review, for the critical items, the management of the risk, by evaluating such factors as: maintenance policy and practices

operating policy and practices change control predictive maintenance technical support vulnerability protective systems. This evaluation can be completed with very little additive study time, using proven and simple word Figure 5 Management of risk.

Likelihood or Vulnerability
per Year Annual Failure Rate (1/MTBF)
Maintenance Policy & Practices

Operating Policy & Practices

Predictive Maintenance

Protective Systems

Technical Support

Care Factor Score

Change Control

Weighting
2

2 3 5 5 3

2 5 5 5 5

1 3 1 1 3

1 1 1 1 1

2 5 5 5 5

5 3 5 5 3 51 1

0.2 3 5 5

3 3 3 3

0.2 2.4 4 5

63 0.8 63 0.8 51 1

per Year

Likelihood (L)

Vulnerability

Care Factor

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models (Figure 5). This allows critical items to be ranked, not only in terms of impact on operations and so on, but also in terms of how well the risk is managed. This approach identifies items where the high relative criticality comes from weaknesses in maintenance practices or hardware, rather than simply on basic potential impact. Following completion, the data can be rapidly sorted in a number of ways for further assessment, depending on the issues to be addressed, such as impact on GMP, maintenance costs or HSE. Analysis of this ranked data enables decisions to be made regarding criticality-cut points.

nance instructions; and specific areas of training). At this stage, the maintenance activities, frequencies and timing are reviewed to agree and confirm that these are beneficial, cost-effective and can be resourced.

avoiding the sticky depths of complex reliability studies.

References
1. Pharmaceutical Engineering Guides for New Facilities, Volume 5: Guide on Commissioning and Qualification First Edition, March 2001. 2. US Food and Drug Administration, Code of Federal Regulations, Title 21, Part 211, Subpart D (2004). 3. British Standards Institution, BS5760 Reliability, Availability, Maintainability and Failure Modes and Effects Analysis (1988). 4. US Department of Defense, Military Standard Procedures for Performing FMEA (Mil-Std-1629), Washington DC (1980).

Maintenance Schedule Implementation

Prior to implementing the agreed maintenance policies, it is beneficial to identify the readiness of the organization and the implications/requirements for implementation. The implementation itself will include the following elements: establish detailed implementation plan and milestones systems preparations (computerized maintenance management system [CMMS] and other documentation) resource preparation including contracted out service (original equipment manufacturer [OEM] or facilities management) implementation of maintenance routines identify appropriate effectiveness measures.

Maintenance Definition Process

The completed criticality analysis is used to guide the development of focussed and effective maintenance routines. Equipment items are identified as: High criticality failure mode and effect analysis (FMEA) studies, with and without failure mode criticality assessment (FMECA) is a well-established technique.3,4 FMECA studies are applied to specific duty requirements to identify appropriate maintenance actions and frequencies. The technique can be timeconsuming if not done in a focussed and efficient way. Medium criticality FMEA studies can be done rapidly using existing generic studies for different equipment types. This speeds up the process considerably and avoids re-invention. Low criticality application of generic policies only or no action required. Best results are achieved by getting the right team in place, with an experienced facilitator leading the process to improve the efficiency of the study and reduce reliance on key operating and maintenance personnel. The studies will identify the following: key failure modes and the effects of the failure appropriate maintenance type appropriate maintenance activities and frequencies other required actions (e.g., operational checks operating/mainte6

Conclusions
Manufacturing equipment must be regularly maintained to ensure that the equipment does not adversely affect the integrity of the drug substance or product; equipment is available when required for production; and to ensure safe and environmentally sustainable operations. Documentary evidence is required to demonstrate that adequate controls are in place to achieve this. Maintenance qualification provides a review of the adequacy of maintenance procedures in place for direct impact systems as well as documenting critical factors relating to calibration, maintenance and cleaning of the equipment. For systems with indirect or no impact, it is possible that efficiencies may be made in the maintenance function. Business criticality analysis and maintenance definition provides a rapid methodology to establish equipment criticality, vulnerability and maintenance strategy. This targeted approach allows quick wins to be identified with the minimum input of time and resources and
PHARMACEUTICAL TECHNOLOGY EUROPE, 17(3), 2025 (2005)