How to Plan Smoke Studies / 기류패턴 확인시험 실시방법

https://www.pharmtech.com/view/how-plan-smoke-studies

How to Plan Smoke Studies

 

irflow visualization studies, or smoke studies, confirm unidirectional airflow patterns in an aseptic processing facility.

Mc_Mon/shutterstock.com

 

This article was published in Pharmaceutical Technology Europe, Volume 30, Issue 5, May 2018.

Airflow visualization studies (i.e., smoke studies) are conducted to confirm unidirectional airflow patterns within an aseptic processing facility. Static studies are intended to document that the airflows within the Class A/ISO 5 zones are unidirectional and cascade out to the zones with lower cleanliness requirements. Dynamic studies should document that airflow within the Grade A/ISO Class 5 filling lines is unidirectional and sweeping down and away from sterile equipment surfaces, container/closure systems, and product. Dynamic studies work to confirm that facility and equipment design, equipment operation, and personnel aseptic manipulations (i.e., interventions) do not disrupt the “first air” (i.e., air exiting the high-efficiency particulate air filters within the Class A zone essentially particle free, in a unidirectional manner) to critical areas where sterile surfaces, materials, and products are exposed.

 

이 기사는 Pharmaceutical Technology Europe, Volume 30, Issue 5, 2018 년 5 월에 출판되었습니다.

 

무균 처리 시설 내에서 단방향 기류 패턴을 확인하기 위해 기류 시각화 연구 (즉, 연기 연구)가 수행됩니다. 정적 연구는 Class A / ISO 5 구역 내의 기류가 단방향이며 청결도가 낮은 구역으로 계단식으로 나뉘어 있음을 기록하기위한 것입니다. 역동적 인 연구에 따르면 A / ISO Class 5 충전 라인의 공기 흐름이 단방향이며 멸균 장비 표면, 용기 / 폐쇄 시스템 및 제품에서 멀리 떨어지거나 멀리 떨어져 있다고 기록해야합니다. 동 역학적 연구는 시설 및 장비 설계, 장비 작동 및 인원 무균 조작 (즉, 개입)이 "첫 번째 공기"(즉, 클래스 A 구역 내에서 고효율 미립자 공기 필터를 빠져 나가는 공기가 본질적으로 입자를 방해하지 않음)를 확인합니다. 무균 표면, 재료 및 제품이 노출되는 중요한 영역에는 단방향 방식으로 자유 롭습니다.

 

Inadequate airflow (e.g., turbulence due to line design issues and first air disruption during interventions) in the critical Grade A zones, where sterile products and components are exposed, could lead to the introduction of contaminants into drug products as they are being filled and stoppered, posing a risk to product sterility.

멸균 된 제품 및 구성 요소가 노출되는 중요한 A 등급 영역에서 부적절한 공기 흐름 (예 : 라인 설계 문제로 인한 난기류 및 개입 중 첫 번째 공기 중단)는 멸균 된 제품 및 구성 요소가 노출되어 마개가 막히면 의약품에 오염 물질이 유입 될 수 있습니다. 제품 불임의 위험이 있습니다. 

 

A product contamination risk can result if first air is disrupted by passing over non-sterile surfaces of equipment, tools, components, or operators on its way to exposed sterile product, components, and equipment. Any viable or non-viable matter on these non-sterile surfaces can be dislodged and introduced as contaminants into the sterile drug product.

장비, 공구, 구성품 또는 작업자의 비 멸균 표면을 노출 된 멸균 제품, 구성품 및 장비로 전달하여 첫 번째 공기가 방해를 받으면 제품 오염 위험이 발생할 수 있습니다. 이들 비 멸균 표면상의 임의의 생존 또는 비 생존 물질은 제거되어 멸균 약물 제품에 오염 물질로서 도입 될 수있다.

 

A successful smoke study report will include a thorough analysis of the study, justifying that satisfactory airflow under static and dynamic conditions was achieved. If the smoke study finds unacceptable air flow (e.g., first air disruption by equipment operation and/or personnel interventions) or turbulence, an investigation should identify the root causes and recommend actions to be taken (e.g., filling line or equipment modification, change in personnel behavior/aseptic technique, adjustment of air velocities). 

성공적인 연기 연구 보고서에는 연구에 대한 철저한 분석이 포함되어 정적 및 동적 조건에서 만족스러운 기류가 달성되었음을 정당화합니다. 연기 연구에서 허용 할 수없는 기류 (예 : 장비 작동 및 / 또는 인력 개입으로 인한 첫 번째 공기 중단) 또는 난류가 발견되면 근본 원인을 파악하고 취해야 할 조치 (예 : 충전 라인 또는 장비 수정, 인원 행동 / 무균 기술, 대기 속도 조정).

 

 

Turbulent airflow may be acceptable in closed systems, such as an isolator, provided that studies demonstrate that acceptable particulate levels can be maintained. Smoke study video recordings are considered data that should be maintained as any other data generated on site. 

연구에 따르면 허용 가능한 미립자 수준이 유지 될 수있는 것으로 밝혀진 경우 난류 기류는 차단기와 같은 폐쇄 시스템에서 허용 될 수 있습니다. 연기 연구 비디오 녹화는 현장에서 생성 된 다른 데이터로 유지되어야하는 데이터로 간주됩니다.

 

 

GMP requirements

Although the FDA good manufacturing practice (GMP) regulations do not specifically refer to smoke or airflow visualization studies, FDA has issued observations using FDA Form 483 and warning letters citing the lack of smoke testing or inadequate smoke testing to establish appropriate airflow that reference the following sections of 21 Code of Federal Regulations (CFR)Part 211, Current Good Manufacturing Practice for Finished Pharmaceuticals (1): 

 

FDA의 GMP (Good Manufacturing Practice) 규정이 연기 또는 기류 시각화 연구를 구체적으로 언급하지는 않지만 FDA는 FDA Form 483 및 연기 테스트 부족 또는 부적절한 연기 테스트 부족을 언급하는 경고문을 사용하여 다음을 참조하는 적절한 공기 흐름을 확립하는 관찰을 발표했습니다. 21 미국 연방 규정 (CFR) 2111 조, 완제 의약품에 대한 현행 우수 제조 관행 (1) :

 

211.113(b) Appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and followed. Such procedures shall include validation of any sterilization process.

211.113 (b) 멸균을 목적으로하는 의약품의 미생물 오염을 방지하기 위해 고안된 적절한 서면 절차를 수립하고 준수해야한다. 이러한 절차에는 멸균 과정의 검증이 포함되어야한다.

 

211.63 Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance.

211.63 의약품의 제조, 가공, 포장 또는 보유에 사용되는 장비는 의도 된 용도와 세척 및 유지 보수를위한 작업을 용이하게하기 위해 적절한 디자인, 적절한 크기 및 적절한 위치에 있어야한다.

 

21 CFR Part 211.113(b) is generally cited when the video shows operator activities are contributing to turbulence or the true air flow cannot be demonstrated based on the poor placement of the smoke source and camera angle. 

21 CFR Part 211.113 (b)는 일반적으로 비디오에서 작업자 활동이 난류에 기여하거나 연기 소스 및 카메라 각도의 열악한 배치로 인해 실제 공기 흐름을 보여줄 수없는 경우에 인용됩니다.

 

21 CFR Part 211.63 is generally cited when the video shows the line design/equipment placements are contributing factors to turbulence.

21 CFR Part 211.63은 일반적으로 비디오에서 라인 디자인 / 장비 배치가 난류에 영향을 미치는 요인을 보여줍니다.

 

 

Elements of a smoke study protocol

Airflow smoke studies should be performed during qualification of new facilities, following changes in facilities impacting the sterile core (e.g., air-handling systems or aseptic processing equipment), and following changes/improvements in aseptic activities/interventions. 

무균 코어에 영향을 미치는 시설 (예 : 공기 처리 시스템 또는 무균 처리 장비)의 변경 및 무균 활동 / 중재의 변경 / 개선에 따라 새로운 시설을 인증하는 동안 기류 연기 연구를 수행해야합니다.

 

The smoke study protocol should clearly define the objectives, responsibilities, tools to perform the study, and acceptance criteria for static and dynamic conditions. 

기류패턴 확인시험 프로토콜은 목표, 책임, 연구 수행 도구 및 정적 및 동적 조건에 대한 수용 기준을 명확하게 정의해야합니다.

 

To ensure a strong smoke study, the following elements should be included in the plan:

강력한 기류 패턴 확인을 보장하려면 다음 요소가 계획에 포함되어야합니다.

• Responsibilities for developing, implementing, reviewing, and approving the smoke studies(기류 패턴의 개발, 구현, 검토 및 승인에 대한 책임)

• A floor diagram of each filling room including details within the filling line and the equipment, carts, etc. in the support areas surrounding the filling line (The floor diagram can mark the general position where the operator will perform each type of intervention, the general position of the smoke source and camera position(s) to effectively capture each intervention. These floor diagrams are helpful to identify to the inspector where the intervention is being performed and the location of the camera because some smoke study views are too close up to clearly show where on the line this is occurring.) (충전 라인 주변의 지지 영역에있는 충전 라인과 장비, 카트 등의 세부 사항을 포함하는 각 충전실의 바닥 다이어그램 (바닥 다이어그램은 작업자가 각 유형의 개입을 수행 할 일반적인 위치를 표시 할 수 있음) 각 연기를 효과적으로 포착 할 수있는 Smog Generator의 위치 및 카메라 위치와 플로어 다이어그램은 일부 기류패턴 확인시험 시 뷰가 너무 가까워서 개입하지 않은 검사관과 카메라 위치를 식별하는 데 도움이됩니다. 이 줄에서 어디에서 발생하는지 보여줍니다.)

• Type of smoke generators to use and smoke source (e.g., water for injection or deionized water heated and combined with liquid nitrogen or dry ice. (사용 및 연기 발생원의 유형 (예 : 주입 용 물 또는 탈 이온수 가열 및 액체 질소 또는 드라이 아이스와 결합)

• Acceptance criteria, as applicable (see following section) (적절한 허용 기준(아래 섹선 참조))

 

• Actions to take if acceptance criteria are not met (e.g., an investigation to determine the root causes and implementing a corrective action and preventive action [CAPA] to eliminate a recurrence of airflow disruption. Note that after implementation of the CAPA a new smoke study is performed.) (허용 기준이 충족되지 않은 경우 취해야 할 조치 (예 : 근본 원인을 파악하고 시정 조치 및 예방 조치 [CAPA]를 구현하여 기류 중단의 재발을 제거하기위한 조사) CAPA를 구현 한 후 새로운 연기 연구는 수행.)

• The process for identifying each intervention shown on the video (e.g., a placard or slide can precede each intervention and/or narration as each intervention is performed). (비디오에 도식 된 각각의 개입을 식별하는 프로세스 (예를 들어, 플래 카드 또는 슬라이드는 각각의 개입이 수행 될 때 각각의 개입 및 / 또는 내레이션보다 우선 할 수있다).

Acceptance criteria include the following:

허용 기준은 다음과 같습니다.

 

• Static conditions within the Grade A filling lines show unidirectional airflow patterns sweep down and/or away from the exposed product, product contact packaging components, and product contact surfaces. (Grade A 충전 라인 내의 정적 조건은 단방향 기류 패턴이 노출 된 제품, 제품 접촉 포장 구성 요소 및 제품 접촉 표면에서 스윕 다운 및 / 또는 멀어지는 것을 보여줍니다.)

• Dynamic conditions within the Grade A filling lines show unidirectional airflow remains stable during interventions with no disruption of first air to critical areas where sterile surfaces, materials, and products are exposed. (Grade A 충진 라인 내의 동적 조건은 멸균 표면, 재료 및 제품이 노출되는 중요 영역으로의 첫 번째 공기의 중단없이 개입 동안 단방향 공기 흐름이 안정적으로 유지됨을 보여줍니다.)

• Air from outside the critical Grade A/ISO Class 5 area is not drawn into the critical zone during interventions. (위험 등급 A / ISO Class 5 영역 외부의 공기는 개입 중에 위험 구역으로 유입되지 않습니다.)

• Sufficient smoke should be generated to allow the smoke to merge with the airflow and visually display its direction.(연기가 공기 흐름과 합쳐지고 방향을 시각적으로 표시 할 수 있도록 충분한 연기가 발생해야한다.)

• The smoke source is positioned to allow sufficient smoke to enter the airflow over the operator and tools (e.g., forceps) during the intervention to visualize the impact of this activity on the airflow. As the operator and tool moves within the Grade A filling line during the intervention, gradually move the smoke source to follow these activities to allow continuous visualization of the impact of the operator’s activities to the first air. (연기 소스는 개입 중에 이 연기가 공기 흐름에 미치는 영향을 시각화하기 위해 충분한 연기가 작업자 및 도구 (예 : 겸자)를 통해 공기 흐름으로 유입 될 수 있도록 배치됩니다. 개입하는 동안 작업자와 도구가 Grade A 충전 라인 내에서 움직일 때, 연기 활동을 서서히 움직여 이러한 활동을 따르십시오. 따라서 작업자 활동이 첫 번째 공기에 미치는 영향을 지속적으로 시각화 할 수 있습니다.)

• Do not generate excessive smoke. The density of the smoke may prevent a clear view of the operator, the intervention, and impact on airflow. (과도한 연기를 발생시키지 마십시오. 연기의 밀도는 작업자의 명확한 시야, 개입 및 공기 흐름에 대한 영향을 방지 할 수 있습니다.)

• All interventions occurring in actual filling operations and simulated in media fills must be accurately simulated in smoke studies. Be prepared to provide a master list of all known interventions for each drug product filling operation by container/closure system on each filling line configuration and the supporting smoke study or smoke studies. (실제 충진 작업에서 발생하고 미디어 충진에서 시뮬레이션 된 모든 개입은 연기 연구에서 정확하게 시뮬레이션되어야합니다. 각 충진 라인 구성 및 보조 연기 연구 또는 연기 연구에서 컨테이너 / 폐쇄 시스템에 의한 각 약물 제품 충전 작업에 대한 모든 알려진 개입의 마스터 목록을 제공 할 준비를하십시오.)

• Include ergonomic considerations; if multiple personnel of different stature (e.g., short vs. tall) perform the same intervention in a different manner and/or require different tools or aids, include this in the smoke studies.(인체 공학적 고려 사항 포함; 키가 다른 여러 인원 (예 : 키가 작거나 키가 큰)이 다른 방식으로 동일한 개입을 수행하거나 다른 도구 나 보조 도구가 필요한 경우이를 연기 연구에 포함시킵니다.)

• All filling line and filling room equipment configuration and placement represent those utilized in current routine processing and media fills. All applicable standard operating procedures and any other reference material that may be necessary to verify the accuracy of the room configurations, equipment operation, and personnel intervention should be referenced or attached, as necessary. (모든 충진 라인 및 충 진실 장비 구성 및 배치는 현재 일상적인 처리 및 매체 충진에 사용되는 것을 나타냅니다. 실내 구성, 장비 작동 및 개인 개입의 정확성을 확인하는 데 필요한 모든 해당 표준 운영 절차 및 기타 참조 자료는 필요에 따라 참조하거나 첨부해야합니다.)

 

Executing the smoke study protocol

Smoke studies are generally not a routine event performed at a recurring fixed timeframe in the same manner. New or additional smoke studies may involve changed or different filling rooms, different interventions, new or different smoke sources, different video cameras, or different personnel, for example. Given these variables and the cost, time, resources, and effort necessary to carry out a successful smoke study, it is best to carry out a rehearsal of these activities to identify any unforeseen barriers or limitations.Consider the following:

연기 연구는 일반적으로 동일한 방식으로 되풀이되는 고정 된 기간에 수행되는 일상적인 사건이 아닙니다. 새로운 또는 추가의 연기 연구는 예를 들어 변경되거나 다른 충전 실, 다른 중재, 새로운 또는 다른 연기 원, 다른 비디오 카메라 또는 다른 인원을 포함 할 수 있습니다. 성공적인 연기 연구를 수행하는 데 필요한 이러한 변수와 비용, 시간, 자원 및 노력을 고려할 때 예상치 못한 장벽이나 한계를 식별하기 위해 이러한 활동을 리허설하는 것이 가장 좋습니다.

 

• Determine where and how the smoke source(s) will be placed within the filling line. Based on space and design limitations, different types/sizes of smoke sources may be needed. (연기 공급원이 충진 라인 내에 배치 될 위치와 방법을 결정하십시오. 공간 및 설계 제한에 따라 다른 유형 / 크기의 연기 원이 필요할 수 있습니다.)

• Practice how the person holding the smoke source will follow the operator performing the intervention to ensure the smoke is always correctly positioned. Common errors occur when the smoke source is not held over the operator as he performs the intervention, not moving the smoke source as the operator moves, and having the smoke source in continuous motion, thus preventing a clear view of the impact of the operator on airflow. (연기 원을 들고있는 사람이 연기자가 항상 올바르게 배치되도록 개입을 수행하는 조작자를 따르는 방법을 연습하십시오. 연기 원이 개입을 수행 할 때 연기 원이 조작자 위에 유지되지 않고, 운영자가 움직일 때 연기 원이 움직이지 않고, 연기 원이 연속 운동을하면서, 운영자의 영향이 명확하게 보이지 않도록하는 일반적인 오류가 발생합니다. 기류.)

• Determine the positions for the camera to capture the operator performing the intervention in its entirety. For some interventions, based on the filling line design and space limitations, it may be necessary to video the activity from multiple angles to clearly show the impact of the intervention on the airflow. (조작자가 전체 작업을 수행 할 수 있도록 카메라의 위치를 결정하십시오. 충진 라인 설계 및 공간 제한에 따라 일부 개입의 경우, 공기 흐름에 대한 개입의 영향을 명확하게 나타 내기 위해 여러 각도에서 활동을 비디오 화해야 할 수도 있습니다.)

Ensure the persons responsible for taking the video have the skills to consider how variables such as distance, angle, lighting, camera movement, and other variables can impact the video to minimize the number of re-shoots necessary to capture the intervention and its impact on airflow clearly. The video shoot should have a director to manage and control all the personnel involved in performing the interventions, positioning the smoke source(s), and the videographer(s) to ensure the event is performed accurately, captured clearly and completely on video or, if not, repeated.

비디오 촬영 담당자가 거리, 각도, 조명, 카메라 움직임 및 기타 변수와 같은 변수가 비디오에 영향을 줄 수있는 방법을 고려하여 중재 및 그 영향에 대한 재 촬영 횟수를 최소화하는 데 필요한 기술을 갖도록합니다. 기류를 명확하게. 비디오 촬영에는 중재 작업 수행, 연기 발생원 배치 및 비디오 그래퍼 (들)와 관련된 모든 인원을 관리하고 제어하여 감독이 있어야 이벤트가 비디오에서 정확하고 명확하게 캡처되거나 그렇지 않은 경우 반복하십시오.

 

Large pharmaceutical companies with numerous and different types of aseptic filling operations and environmentally controlled support rooms may have communication and coordination challenges under some situations, such as when numerous smoke study teams work simultaneously, at times, around the clock to complete all smoke studies during the firm’s plant shutdown or when private smoke testing contractors and/or personnel from other corporate divisions or sites are brought in to assist in the smoke studies. Managing these diverse groups, some of which may have never worked together and may have differing views about smoke studies, will require close quality assurance (QA) oversight to ensure consistent implementation of the smoke study protocols. 

수많은 종류의 무균 충전 작업과 환경 제어식 지원실이있는 대규모 제약 회사는 일부 연기 연구팀이 24 시간 내내 동시에 모든 연기 연구를 완료하기 위해 동시에 일할 때와 같은 일부 상황에서 의사 소통 및 조정 문제를 겪을 수 있습니다. 회사의 공장 폐쇄 또는 개인 연기 테스트 계약자 및 / 또는 다른 회사 부서 또는 현장의 직원이 연기 연구를 돕기 위해 들어온 경우. 연기 그룹에 대해 서로 협력 해 본 적이없고 연기 연구에 대해 다른 견해를 가질 수있는 이러한 다양한 그룹을 관리하려면 연기 연구 프로토콜의 일관된 구현을 보장하기 위해 정밀한 품질 보증 (QA) 감독이 필요합니다.

 

Ensure the persons responsible for taking the video have the skills to consider how variables such as distance, angle, lighting, camera movement, and other variables can impact the video to minimize the number of re-shoots necessary to capture the intervention and its impact on airflow clearly. The video shoot should have a director to manage and control all the personnel involved in performing the interventions, positioning the smoke source(s), and the videographer(s) to ensure the event is performed accurately, captured clearly and completely on video or, if not, repeated.

비디오 촬영 담당자가 거리, 각도, 조명, 카메라 움직임 및 기타 변수와 같은 변수가 비디오에 영향을 줄 수있는 방법을 고려하여 중재 및 그 영향에 대한 재 촬영 횟수를 최소화하는 데 필요한 기술을 갖도록합니다. 기류를 명확하게. 비디오 촬영에는 중재 작업 수행, 연기 발생원 배치 및 비디오 그래퍼 (들)와 관련된 모든 인원을 관리하고 제어하여 감독이 있어야 이벤트가 비디오에서 정확하고 명확하게 캡처되거나 그렇지 않은 경우 반복하십시오.

 

Large pharmaceutical companies with numerous and different types of aseptic filling operations and environmentally controlled support rooms may have communication and coordination challenges under some situations, such as when numerous smoke study teams work simultaneously, at times, around the clock to complete all smoke studies during the firm’s plant shutdown or when private smoke testing contractors and/or personnel from other corporate divisions or sites are brought in to assist in the smoke studies. Managing these diverse groups, some of which may have never worked together and may have differing views about smoke studies, will require close quality assurance (QA) oversight to ensure consistent implementation of the smoke study protocols. 

수많은 종류의 무균 충전 작업과 환경 제어식 지원실이있는 대규모 제약 회사는 일부 연기 연구팀이 24 시간 내내 동시에 모든 연기 연구를 완료하기 위해 동시에 일할 때와 같은 일부 상황에서 의사 소통 및 조정 문제를 겪을 수 있습니다. 회사의 공장 폐쇄 또는 개인 연기 테스트 계약자 및 / 또는 다른 회사 부서 또는 현장의 직원이 연기 연구를 돕기 위해 들어온 경우. 연기 그룹에 대해 서로 협력 해 본 적이없고 연기 연구에 대해 다른 견해를 가질 수있는 이러한 다양한 그룹을 관리하려면 연기 연구 프로토콜의 일관된 구현을 보장하기 위해 정밀한 품질 보증 (QA) 감독이 필요합니다.

Smoke study final report

The smoke study report review process should not lose focus that a key element of the review is the video itself and not principally the unexecuted protocol that contains all the expectations. Upon execution, if the video does not clearly and unequivocally show the adequacy of airflow when interventions were performed accurately on the filling line set-up as currently used, acceptance criteria have not been met. The review of all the static and dynamic smoke study videos should involve subject matter experts (SMEs) from the various departments involved to ensure all depictions in the videos accurately represent current practices. 

연기 연구 보고서 검토 프로세스는 검토의 핵심 요소가 비디오 자체이며 원칙적으로 모든 기대치를 포함하는 미 실행 프로토콜이 아니라는 데 초점을 잃지 않아야합니다. 실행시, 현재 사용 된 채움 라인 설정에서 중재가 정확하게 수행 될 때 비디오가 공기 흐름의 적절성을 명확하고 명확하게 나타내지 않으면 수용 기준이 충족되지 않은 것입니다. 모든 정적 및 동적 연기 연구 비디오를 검토하려면 비디오의 모든 묘사가 현재 관행을 정확하게 표현할 수 있도록 관련 부서의 SME (Subject Matter Expert)가 참여해야합니다.

 

The final QA review to assess compliance with acceptance criteria can be challenging and may benefit by having additional reviews by other QA and/or SMEs not actively involved in producing the smoke study. Having a separate set of reviewers to critically review and, as necessary, challenge any views that are not clear or subject to more than one interpretation, may pick up weaknesses not apparent to the initial reviewers, which are the type of weaknesses that may be detected by a regulatory inspector. 

수락 기준 준수를 평가하기위한 최종 QA 검토는 까다로울 수 있으며 연기 연구 생산에 적극적으로 참여하지 않은 다른 QA 및 / 또는 SME의 추가 검토를 통해 이익을 얻을 수 있습니다. 별도의 검토 자 집합을 비판적으로 검토하고 필요에 따라 명확하지 않거나 하나 이상의 해석에 영향을 미치는 모든 견해에 대해 이의를 제기하면 발견 될 수있는 약점 유형 인 초기 검토 자에게는 명백하지 않은 약점을 찾을 수 있습니다. 규제 감독관이

Non-airflow issues evaluated in smoke studies

Static and dynamic smoke study videos may provide many different views and close-up views within the sterile core that are not visible or clearly visible through the view windows or cameras into these areas. These views can identify other GMP issues for a regulatory inspector to pursue. For example, a clear view of the aseptic technique used in complex interventions could lead to further review of the technique for reproducibility as practiced currently. When viewing the condition of gowning and compliance with gowning requirements, any differences with current gowning practices will be evaluated. A view showing the facility and equipment complexity of design, age, and surface condition (e.g., excessive number of scratches or deep scratches/gouges, deterioration, rust) can lead to questions about how these surface conditions may impact the ability of current practices to consistently and effectively clean, sanitize, and sterilize these surfaces. Questions about preventive maintenance and part replacement practices in these critical areas may also be pursued.

정적 및 동적 연기 연구 비디오는 멸균 코어 내에서 뷰 윈도우 또는 카메라를 통해 이러한 영역으로 보이지 않거나 명확하게 보이지 않는 많은 다른 뷰 및 근접 뷰를 제공 할 수 있습니다. 이러한 관점은 규제 감사관이 추구해야 할 다른 GMP 문제를 식별 할 수 있습니다. 예를 들어, 복잡한 중재에 사용되는 무균 기술에 대한 명확한 견해는 현재 실행되는 재현성 기술에 대한 추가 검토로 이어질 수 있습니다. 가운 상태와 가운 요구 사항 준수를 볼 때 현재 가운 관행과의 차이점이 평가됩니다. 설계, 수명 및 표면 상태의 시설 및 장비 복잡도 (예 : 과도한 수의 흠집 또는 깊은 흠집 / 거품, 악화, 녹)을 보여주는 뷰는 이러한 표면 상태가 현재 관행의 능력에 어떤 영향을 줄 수 있는지에 대한 질문으로 이어질 수 있습니다. 이러한 표면을 일관되고 효과적으로 세척, 소독 및 멸균합니다. 이러한 중요 영역의 예방 유지 보수 및 부품 교체 관행에 대한 질문도 추구 할 수 있습니다.

 

QA review of the smoke studies should not be limited to airflow issues but to the entire content of the video to ensure all GMP issues have been addressed, including those not directly related to airflow.

연기 연구에 대한 QA 검토는 공기 흐름 문제로 제한되지 않고 공기 흐름과 직접 관련되지 않은 문제를 포함하여 모든 GMP 문제가 해결되도록 비디오의 전체 내용으로 제한되어야합니다.

Conclusion

As is the case with media fills, smoke studies only document the conditions occurring at the time the studies were performed. QA and production department oversight should ensure the controls displayed in the smoke studies represent current practices used by all the other personnel performing similar activities but not involved in the smoke studies. Systems should be in place to detect, investigate, correct, and prevent recurrence of any variance from these controls and, as necessary, repeat the smoke study. 

미디어 채우기의 경우와 마찬가지로 연기 연구는 연구 수행 당시에 발생한 조건 만 기록합니다. QA 및 생산 부서 감독은 연기 연구에 표시된 통제가 다른 활동을 수행하지만 연기 연구에 관여하지 않는 다른 모든 직원이 사용하는 현재 관행을 나타내도록해야합니다. 이러한 컨트롤에서 발생하는 편차의 감지, 조사, 수정 및 재발을 방지하고 필요에 따라 연기 연구를 반복 할 수있는 시스템을 갖추어야합니다.

 

This type of smoke study review and preparation can make the regulatory inspector’s review of smoke studies a relatively uneventful and routine step of the inspection, with the inspector generally satisfied with the videos.

이러한 유형의 연기 연구 검토 및 준비를 통해 규제 관리자의 연기 연구 검토는 비교적 사건이없고 일상적인 검사 단계가되며, 검사자는 일반적으로 비디오에 만족합니다.

Reference

1. CFR Title 21, Part 211.

About the Author

Manuel M. Garza is a principal consultant with PAREXEL Consulting, a subsidiary of PAREXEL International, manuel.garza@parexel.com.

Article Details

Pharmaceutical Technology Europe
Vol. 30, No. 5
May 2018
Pages: 38–41

Citation 

When referring to this article, please cite it as M. Garza, "How to Plan Smoke Studies," Pharmaceutical Technology Europe 30 (5) 2018.