HVAC validation in Pharmaceutical industry.

           HVAC VALIDATION IN A NUTSHELL

In the series as I promised this is new article on HVAC validation for pharma foxes. It should be noted that my articles are especially for those peoples who are very ambitious and searching new opportunities on upper levels.

 HVAC means heating ventilation and air conditioning unit. This is an important/integral function of pharmaceutical industry and plays a very sensitive role for controlled zones, recommended as per Federal standard 209(E), ISO 14644, European GMP and British standards. The credibility of HVAC depends on its proper validation. As per USFDA regulation the validation may be defined as

 “A documented programme that provides a high degree of assurance that a specific process, method and system will consistently produce a result meeting to the predetermined/anticipated acceptance criteria.”

In HVAC Heating (from boiler), Ventilation (To provide fresh air for breathing) and Air conditioning  unit zones are covered and now need a well optimized validation strategy to accomplish the mandatory requirements of national and International regulations. The validation programme is conducted through a protocol. Following 10 parameters are validated.

1. Air flow pattern: This parameter is validated by burning Titanium tetra chloride stick and keeping the burning stick in front of air handling unit. Make the chart diagram of smoke movement.

 2. Air velocity and changes per hour in the room: This is carried out as following

2.1 Air Velocity: Divide the HEPA filter into four hypothetical grid and record the air velocity at the center of each grid by Velometer. Calculate the average velocity. For class 100 zone limit is 90 feet/minute.

2.2 Changes per hour: Changes per hour is calculated using following frormulae

Changes per hour:       Total air change

                               Total volume of the room

For class 100 limit is 100 cycle/hour.

3. HEPA/ULPA filter leak test: Check the velocity of air by placing Velometer at all corners of air handling unit. If speed of air is not crossing the  prefixed air speed limit at any point then there is no leakage in HEPA filter.

4. Particle count: Check the particle count of room “at rest” and “in operation” ( after at least one hour routine work) position.

 

5. Viable monitoring: Place the petrisish in the air sampler and operate the sampler as per corresponding sop and observe the microbial load. For class 100 limit is < 1.

6. Filter integrity test (DOP/PAO test): DOP (Di octyl phthalate) aerosol was previously used but due to the carcinogenic nature it was replaced by PAO (Poly alpha olefin) in 2001. Generate the aerosol by aerosol generator at 20 psi at supply duct in the AHU. Stabilize for 5 minute and ensure that 100% upstream concentration is achieved at the all terminals of HEPA.

7. Pressure difference: This parameter is validated by checking pressure difference with the help of Manometer in the room and from one room to another room.

8. Recovery (temperature and humidity): This parameter is validated when humidity/temperature of the zone is within limit. First shut down the AHU then increase the humidity upto a suitable level (usually 75%) by spraying hot water in the zone. Now operate the HVAC system and count the time taken to reduce humidity within the acceptance criteria. For the Temperature recovery shut down the AHU and increase the temperature (usually 40ºC) of the specified zone with the help of blower. Start the AHU and record the time taken by AHU to reduce the temperature within acceptance criteria.

9. Temperature and humidity uniformity test: This parameter is validated with the help of calibrated Thermometer and calibrated Hygrometer by putting them in different locations and observing the temperature and humidity in running AHU position as specified in protocol.

10. Fresh air determination test: Calculate the fresh air intake by Dumper in the room and total air change per pour.

% Fresh air intake = The intake fresh air

                                 Total air change

 After successful completion of validation, validation report is prepared and approved from the QA head. If any abnormality is observed during validation programme an appropriate action is taken as per the corresponding Standard Operating procedure of the organization. 

Clean room zones as per different Regulations: There are mainly 4  guidelines on clean room zones, FED std 209(E), ISO 14644, EU GMP and British std. It should be noted that particles of size ≥0.5µ and ≥5µ are considered in pharma industry.

 

FED std 209(E): For Pharmaceutical industry there are 4 zones as following. FED std is cancelled by general service administration USA in 2001as per the recommendation of Institute of environmental science and technology USA. Still FED std is used in pharmaceutical industry in some countries.

Class	≥ 0.5µ/feet3	≥ 5µ/ feet3	Air changes/hour	Microbes
100	100	0.7	100	< 1
1000	1000	7	100	<10
10000	10000	70	50	<100
100000	100000	700	20	<200

ISO 14644: This is globally accepted and came into effect after Federal standard expiration. All zones are segregated from class 1 to class 9.Class 5 to 8 for Pharmaceutical industry and remaining for Electronics and other industries.

Class	≥ 0.5µ/meter3	≥ 5µ/meter3
5	3520	29
6	35200	293
7	352000	2930
8	3520000	29300

 

EU GMP: EU GMP is very popular in pharma industry. It should be noted that all the aforementioned/below zones are equivalent to each other.

 

Class	At rest (per meter3)		In operation (per meter3)
	≥0.5µ	≥ 5µ	≥0.5µ	≥ 5µ
A	3520	20	3520	20
B	3520	29	352000	2900
C	352000	2900	3520000	29000
D	3520000	29000	N/A	N/A

 

 

 

 

 

 

 

Frequently asked questions for QC/QA manager level in pharma industry

Preamble: An interview is a very special occasion for every jobseeker. Usually everybody makes preparation above/below par as per his perception/IQ level. Among the crowd only few lucky guy cross the hurdle while others effort remains square one…!. Generally jobseekers are not aware of their coming viva-voce scruitinization criteria which results into a sure failure. Recruiters ask mostly what you have mentioned in your Resume. Following are the prototype questions that are frequently being asked in chronological order for Manager QC/QA level positions in API/Formulation industry. Generally there are three rounds that are conducted.

A. Preliminary Round/Telephonic round:

In this round a brief discussion is organised and formal/mini technical questions are being asked depending on case to case. This is also called filter Round. Maximum peoples fate is decided in this Round.

B. Technical Round: This is conducted vis a vis in front of a group of expert’s panel.

1. Tell me something about yourself/ How can we know about you?.

2. What’s Quality policy of your organization?.

3. How many peoples are reporting to you and to whom do you report?.

4. What’s the maximum team size of peoples you have handled?.

5. What can you do for us/ How can you help us?.

6. What is a Quality product?.

7. What’s OOS, OOT,OOE explain in detail ?.

8. What is 21 CFR?explain in detail specially part 11 and 58.

9.  Explain class I, II & III solvent with example and limit.

10. Explain stability zones and stability procedures.

11. Explain type of analytical validation/verification in detail.

12. Calibration procedure for HPLC,GC, FTIR,UV-vis spectrophotometer, Dissolution,
      Disintegration apparatus.

13. Explain ANDA and it’s procedure in India and USA.

14. Explain clean room and it’s classification as per Fed std 209(E), ISO 14644 and EU GMP.

15. Explain air lock system in detail.

16. Why/when to validate/verify a compendial/non compendial method.

17. What’s your current job responsibility?.

18. What were your responsibilities during FDA/GMP/other inspections?.

19. What is the training procedure in your organization?.

20. Explain L1,GLP/cGMP/ICH Quality guideline/Drug and Cosmetic act,  PIC/S, MHRA,
     ANVISA  etc Regulations.

21. Explain Deviation, CAPA and Change Control.

22. How will you develop analytical method for a new compound?.

23. Explain SOR, HPLC, GC, Surface area analyser/Particle size analyser Principle and operation
      procedure.

24. What’s Autoclave and Sterlity validation procedure?.

25. What are Gram positive and Gram negative bacteria?.

26. Explain Bioindicator, environmental monitoring, sterility procedures and trace elements.

27. What is Water system validation and cleaning validation procedures?.

28. What are 7 QC tools?.

29. What’s APR/PQR and BMR/BPR?.

30. What’s DMF and it’s filing procedure?.

31. What’s master validation plan and process validation?.

32. What is the complaint handling procedure in your organization?.

33. What’s drug recall give classification.

34. Explain Validation and operation of HVAC system .

35. What’s QBD, Quality risk management, HACCP,FTA,PK,PAT,HAZOP,FMEA?.

36. What is GAP analysis?.

37. What’s Quality management system in your organisation?.

38. What’s carryover in HPLC/GC and how will you control this?.

39. How will you perform the Qualification of an instrument.

40. Why do you want to leave your current organization?.

 C. HR Round:

If technical round is successful then this round is conducted. In this round  personal Questions are discussed and eventually bargaining on salary takes place. Upon successful mutual agreement offer letter is either issued immediately or later.