1. INTRODUCTION:

A Tray Dryer is an equipment in which trays are placed in shelves on each other. Tray Dryer is used where heating and drying are critical parts of the manufacturing processes in industries such as Chemicals, Dyestuff, Pharmaceutical, Food Products, Colours etc. The materials placed in the trays to be dried are moreover wet or solid. Electric Heaters or Steam in radiator coils are installed within. A control panel is to set the temperature and other parameters of the dryer. These dryers are available in Mild Steel, Stainless Steel¹. For the best drying results in conventional processes Tray Dryer is used. The cabinet is double walled with single or two doors and provided with gasket. The high-density fibre glass wool insulation material is filled in gap between two walls to avoid heat transfer. Trays made-up of Stainless steel are placed on the portable trolleys.

The control panel board, Digital temperature controller cum indicator, process timer etc are provided on Tray Dryer. The capacities ranging from 6, 12, 24, 48, 96, 192 trays are available in Tray Dryer. Standard and GMP models with SS 304/SS 316L Internals and Externals are available in Tray Dryers².

The Tray Dryer is fabricated according to FDA and CGMP guidelines. This guideline has planned to help manufacturers implementing modern quality systems and risk management approaches to meet the requirements of the current good manufacturing practice (CGMP) regulations (2l CFR parts 210 and 211). The guidelines also explain how manufacturers implementing such quality systems in full compliance with parts 210 and 211. This guideline is not planned to place new expectations on manufacturers, nor to replace the CGMP requirements³.

Vaporization of water in the product is normally called drying, so the heat of vaporization must be provided. To remove the vapor away from the product, airflow is also required. The drying rate is better as it removes moisture from the product surface when the supplied humidity of hot air is low⁴.

Qualification of the Tray Dryer was done According to the flow chart given below:

Figure 1: Flow chart for the validation of equipment

1.1 User Requirement Specification (URS):

The User Requirement Specification (URS) is an important document that mention all the requirements that are specific to the user that include equipment, facility, systems in relationships of function, operability, appropriate standards, functions that will be carried out, and the data on which the system will perform. URS is practised under Functional requirements and Non-functional requirements.

1.1.1 Functional requirements:

Define the complete knowledge of how the plant must operate which include operational steps, operator actions, calculations, data manipulation, processing, and several other specific functionalities.

1.1.2 Non-functional requirements:

It includes overall the structure of the equipment, limitations and operation carried out by the equipment.

The URS is the point at which the user’s requirements are defined with sufficiently precise detail to allow vendors to produce tenders for the workplace and involve a feasibility study⁶.

The needs of the manufacturing department are specified by employing URS. URS are written for the production procedure of a pharmaceutical product. To states the measurements of the equipment URS is an important document. The achievement of the good project is by preparing good URS. If the URS is not prepared for the projects it may lead to lot of changes later, and as well start-up time, cost as well as both. To create a URS some companies, use the services of the exterior resources.

URS mainly includes:

· FDA requirement

· Technical and economic demand

A. FDA Requirement:

FDA requirements are fulfilled by URS which is the key feature to develop detailing document for all the technical system. The URS is an important document require for the authorizing phase as well. It provides the foundation for an offer to the suppliers.

B. Technical and Economic demand:

Technical as well as economic requirements are documented in the URS for the technological organization. As URS is not collected merely for the validation it covers more aspects than only the FDA requirement⁷.

1.2 Factory Acceptance Test (FAT):

Factory Acceptance Test (FAT) is an official test and the inspection work process that performed at the manufacturer when the system or facility is fully fabricated and assembled prior to the delivery. The FAT is to test the function and capacity of the products and system at the factory⁸.

1.3 Site Acceptance Test (SAT):

Site Acceptance Test (SAT) is performed at the site, before the system is installed at the permanent operating position. The SAT is to test and check functions with other interfaces on the site⁹.

1.4 Installation Qualification (IQ):

The installation and configuration of a system is verified by Installation Qualification Protocol. IQ Protocol is the documented evidence that the equipment has been installed properly adhering to all key aspects of the installation, approved design intentions and manufacturers recommendation. When Installation of equipment has been done, approval of the necessary procedures, or the training of apposite personnel have to be done. IQ protocols must be accepted before protocol execution. The validation package retains a transcript of the unexecuted protocol. The System Owner and Quality Assurance must favour the unexecuted convention, while executed a convention must be marked by the analyser and checked on by the System Owner and Quality Assurance¹⁰.

1.5 Operational Qualification (OQ):

The Operational Qualification in simple terms means that the operation of the system meets the requirements as in URS. The OQ Protocol is the document which includes test cases in order to confirm the proper operation of the system. The URS mention the test requirements OQ. OQ is a crucial step which is performed before the system is ready for use. OQ can be linked to IQ and PQ based on complexity of the system¹⁰.

1.6 Performance Qualification (PQ):

Building confidence through suitable testing that the completed product or process made by a predefined procedure meets all release requirements for functionality and safety and that operations are compelling and predictable. The PQ protocol is a document that proves that a system qualifies that a system gratifies the defined requirements in the production environment¹⁰.

2. METHODOLOGY:

2.1 User Requirement Specification (URS):

URS for the tray dryer was prepared according to cGMP and FDA guidelines. URS was prepared according to the in house requirement.

1. Name of the Equipment: Tray Dryer

2. Equipment Make / Model: cGMP

3. Purpose of the Equipment:

Drying of wet granules, Uniform dried granules formation, Remove the moisture from the Powders.

4. Capacity / Output:

Gross volume: 229500 cm³

Working volume: 8400 cm³each; 8400 cm³ X 5 Trays

5. Process Requirements:

· Occupancy hours: 10 hours

· Material of construction

SS316 – Product contact part

SS304 – Non-contact part

· Number of Trays:

Trays with dimensions 80 x 42 cm: 5

Trays spare of same dimensions: 2

· Vent:

On the top at the left side of the equipment

· Preferable method of cleaning:

Clean in place and manual

· Available area for installation:

It will be positioned in the provided area of size 105 x 70 x 102 cm

· Environmental conditions:

Operating temperature: 50°C to 100°C

6. Automation and Control system:

Table 1:Automation and Control system

S. No	Component (s)	Required (yes / no)	Description
1.	Motor	Yes	½ HP
2.	Fan	Yes	1 fan with 500rpm
3.	Heating coil	Yes	3 Coil, 1 left 1 right and 1 middle
4.	Temperature sensors	Yes	2 sensors
5.	Alarms and Warning	Yes	After attending the given temperature or complete drying, interlocking with product temperature sensors
6.	MMI / HMI and PLC Details	Yes	Auto / Manual / Recipe / Maintenance / WIP modes required.
7.	Powder Button	Yes	Button with red colour and light indicating when it ON

MMI: Man-Machine Interface; HMI: Human Machine Interface; PLC: Programmable Logic Controller; WIP: Work in Process / Progress

7. Other Requirements:

Table 2: Other Requirements

S. No	Description	Purpose
1.	Two Spare trays	Standby in case of damage
2.	Meshes cover for the motor	To protect the working person
3.	Stainless steel 304 Door Handle	To open
4.	Silicone covering around the Door	To prevent the airflow and maintain temperature.
5.	Ammeter and Voltmeter on electrical panel door	To access the current flow

8. Safety features:

Table 3: Safety features

S. No	Safety features	Required (yes / no)	Description
2.	Earthing	Yes
3.	Noise level	Yes	Sound reduction 70 to 75 dB

9. Documentation:

Table 4: Documentation

S. No	Title	Required (yes / no)	Description
1.	Material of construction Certificate (MOC)	Yes	Certificate shall be provided for contact, Non-contact pants
2.	Performance Test Certificates	Yes	No load running trials and load trials required at site
3.	Qualification Document (DQ, IQ, OQ and PQ documents)	Yes	Provide the qualification documents like IQ OQ PQ
4.	Operation and Maintenance Manual	Yes	Required 2 sets
5.	Drawing GA Drawing P and ID Drawing Electrical	Yes Yes Yes	Required 2 sets
6.	Others		Any other if there is value addition to that other than stated in this URS

10. Other requireents:

Table 5: Other requirements

S. No	Title	Required (yes / no)	Description
1.	Training	Yes	Required on operation and maintenance of PLC
2.	Inspection at Vendor’s end (FAT)	Yes	Allow to inspect at your site before dispatch of equipment
3.	Technical support	Yes	Required for trouble shooting and spares list
4.	Others	Yes	Required warranty certificate of equipment

11. URS Acceptance by the vendor:

The User Requirement Specification has been discussed and agreed upon. We hereby declare that we will supply the equipment as per above laid down specification

Name of the Vendor		Signature / Date

	Prepared by	Approved by	Authorized by
Designation
Name
Sign and date

2.2 Installation Qualification (IQ)¹¹:

Installation Qualification was prepared as per the protocol mentioned in URS. Installation Qualification is conformity with installation specification, equipment manuals schematics and engineering drawing ensuring that all major processes of the equipment. IQ is done to check that the equipment has been introduced as per makers suggestion in an appropriate way and put in a situation reasonable for its planned reason⁵.

2.2.1 Objective:

To demonstrate that the Tray Dryer installed in the Department of Pharmaceutics, PG Lab 2, conforms to the purchase specification and the manufacturers literature, and to document the information that the equipment meets specifications.

2.2.2 Scope:

For Installation and Qualification of a New Laboratory Tray Dryer

2.2.3 Responsibility:

Supervisor of the department where the Tray Dryer is located is responsible for writing the protocol, supervising the performance of the IQ, verifying the data and writing the IQ report.

QA department for approving the protocol, reviewing, approving the date and providing conclusions.

2.2.4 Systems / Equipment:

i. Name of the Equipment: - Tray Dryer

ii. Equipment Make / Model: - cGMP

iii. Purpose of the Equipment: -

Drying of wet granules, Uniform dried granules formation, Remove the moisture from the Powders.

iv. Material of construction of product: -

· SS316 – Product contact part

· SS304 – Non-contact part

v. Number of Trays: -

Trays with dimensions 80 x 42 cm: - 5

Trays spare of same dimensions: - 2

vi. Number of Motor: - 1 Motor ½ HP

vii. Number of fan: - one fan

viii. Temperature sensors: - 3

ix. Heating coil: - 2

x. MMI / HMI / PLC: - controlling system

xi. Power button

xii. Alarm

xiii. Ammeter and Voltmeter

xiv. Earthing

xv. Silicone covering around the Door

xvi. Meshes cover for the motor

2.3 Operational Qualification (OQ) [11]:

2.3.1 Objective:

To determine that the Tray Dryer installed in building of Manipal College of Pharmaceutical Science (Department of Pharmaceutics PG Lab 2), operates according to specifications

2.3.2 Equipment and Documents:

This is done to give a high level of affirmation that the gear capacities as proposed. Operational Qualification ought to be directed in three phases:

· Component Operational Qualification, of which adjustment can be viewed as a large part.

· System Operational Qualification to decide whether the whole framework works as a coordinated entirety.

· Process Performance Qualification: This checks the framework is repeatable and is reliably creating a quality item⁵.

2.3.3 Procedure:

Preparation of the granules (without drug) by using the following formula

Table 6: Formula

Ingredient	Quantity (g)
HPMC	4.4
MCC	13.3
Lactose	0.8
Talc	0.4
Mg. Stearate	0.8

Granules prepared for performing the OQ Studies.

2.4 Performance Qualification (PQ) [11]:

2.4.1 Objective:

To determine that the Tray Dryer installed in building of Manipal College of Pharmaceutical Science (Department of Pharmaceutics PG Lab 2), executes as proposed by over and again running the equipment on its expected schedules and recording all pertinent data and information for temperature distribution studies and load setups which will be tried and tested. Results must show that execution reliably meets pre-determined under ordinary conditions, and where proper for worst circumstances.

2.4.2 Equipment and Documents:

Before beginning the performance validation, SOPs for every test method, the data to be recorded, and the criteria for acceptance should be prepared and approved. Thermocouple location Diagrams for each trial. Charts for the time and temperature recording.

2.3.3 Procedure:

Preparation of the granules by using the following formula

Table7: Formula

Ingredient	Quantity (mg)
Diclofenac Sodium	50
Microcrystalline Cellulose	40
Sodium Starch Glycolate	20
Lactose	80
Talc	2
Mg. Stearate	1.6
Colloidal Silicon dioxide	2

Granules prepared with the drug (actual batch) for performing the PQ Studies.

Figure 2: Granules

Loss on Drying (LOD)

Formula:

Inital weight of sample – Weight of sample after stying

LOD = ---------------------------------------------------------------------------

Inital weight of sample

The experiment was carried out at 70⁰c for 1 hour 30 min at three different places in the equipment i.e. top, middle and bottom as show below

Figure 3: Tray Dryer

3. RESULT AND DISCUSSION:

3.1 Installation Qualification (IQ):

Installation Qualification of tray dyer was done by preparing a check list of the parts and functions as specified in URS. The equipment was inspected and accordingly Yes or No was selected in the check list.

Tick Yes / No for the following:

Table 8: Procedure

i.	Equipment Model cGMP	þ Yes	□ No
ii.	Material of construction of product
	Product contact part - SS316	þ Yes	□ No
	Non-contact part - SS304	þ Yes	□ No
iii.	Number of Trays
	Trays with dimensions 80 x 42 cm 5	þ Yes	□ No
	Trays spare of same dimensions 2	þ Yes	□ No
iv.	One motor ½ HP	þ Yes	□ No
v.	One fan	þ Yes	□ No
vi.	Temperature sensors 3	þ Yes	□ No
vii.	Heating coil 2	þ Yes	□ No
viii.	MMI / HMI / PLC controlling system	þ Yes	□ No
ix.	Power button	þ Yes	□ No
x.	Alarm	□ Yes	þ No
xi.	Ammeter and Voltmeter	þ Yes	□ No
xii.	Earthing	þ Yes	□ No
xiii.	Silicone covering around the Door	þ Yes	□ No
xiv.	Meshes cover for the motor	þ Yes	□ No
xv.	Noise level 70-75 dB	þ Yes	□ No
xvi.	Material of construction Certificate (MOC)	þ Yes	□ No
xvii.	Inspection at Vendor’s end (FAT)	þ Yes	□ No
xviii.	Drawing 2 sets	þ Yes	□ No

Report:

Installation Qualification was carried out successfully and the equipmenst is now ready for Operational Qualification.

3.2 Operational Qualification (OQ):

Operational Qualification of tray dryer was done by performing following studies

· Challenge test for set Temperature: In this study, the equipment was set at different temperature, a calibrated thermometer was used to carry out three trials to confirm the set temperature of the equipment. Obtained results are tabulated as shown in Table 9.

Table 9: Challenge test for set Temperature

Set Temperature (°C)	Actual Observed Temperature (°C)
Set Temperature (°C)	Trial 1	Trial 2	Trial 3
50	49	49	48
55	55	53	54
60	59	58	58
65	63	63	64
70	71	69	70
75	77	75	76
80	82	80	80
85	84	83	84

· Time required to reach temperature: In this study, the time was noted down after reaching the temperature and the results were tabulated as shown in Table 10.

Table 10: Time required to reach set temperature

Temperature (°C)	Time
50 -55	1 min 30sec
55 -60	2 min 00sec
60 -65	2 min 15 sec
65 -70	2 min 40 sec
70 -75	2 min 53 sec
75 -80	5 min 12 sec
80 -85	1 min 42 sec

· Temperature distribution study: In this study, the temperature of the equipment was set at three different temperature, at three different position and a calibrated thermometer was used to carry out three trials to confirm the set temperature of the equipment and the results were tabulated as shown in Table 11.

Table 11: Temperature Distribution Study

Trial Number	Set Temperature (°C)	Actual Observed Temperature (°C)
Trial Number	Set Temperature (°C)	Top	Middle	Bottom
Trial 1	50	48	50	50
	70	68	69	70
	80	79	80	80
Trial 2	50	48	50	50
	70	69	70	69
	80	78	79	80
Trial 3	50	49	49	50
	70	68	70	70
	80	79	80	79

Calibration of Temperature: In this study, the temperature was checked by used calibrated thermometer as showed in below fig. 4 and 5 for 70°C both on the equipment as well as thermometer showed the same temperature.

Figure 4: Thermometer

Figure 5: Tray Dryer Temperature indicater

Report:

Operational Qualification carried out successfully and the equipmenst is now ready for Performance Qualification.

3.3 Performance Qualification (PQ):

Performance Qualification of tray dryer was done by performing following study. Prepared granules were used to determine the Percentage Loss on Drying. Granules were weighed with the dish and calculated the weight of granules (i.e. W3). This weight is before the drying, granules were kept for drying in the tray dryer and the weight of granules was noted after drying. The following calculation were done, one of the calculation is given below.

Calculation:

Weight of the Dish (W1): 30.168 g

Weight of the Dish and Granules (W2): 32.168 g

Weight of the Granules (W3): W2 – W1; 32.168 g – 30.168 g = 2 g

Weight of the Dish and Granules After drying (W4): 32.135 g

Weight of the dried Granules (W5): W4 – W1; 32.135 g – 30.168 g = 1.967 g

LOD % = X 100; X 100 = 1.65

Table 12: Loss on Drying

LOD (%)	Top	Middle	Bottom
A	1.65	1.85	1.95
B	1.55	1.95	1.95
C	1.7	1.9	1.95

Reporting:

The equipment performed satisfactorily, Tray dryer is thus qualified and can be used for regular experimental or research activities.

4. CONCLUSION:

Qualification of the equipment is a regulatory requirement so that medicinal products manufactured using these equipment shall produce a product always meeting predetermined specifications. Therefore, the study was carried out on New Laboratory Tray Dryer which was fabricated according to the URS document. Equipment qualified all the process steps successfully such as FAT, SAT, IQ, OQ and PQ. The New Laboratory Tray Dryer qualifies and ready to use for the manufacturing process or experimental purpose.

5. REFERENCES:

1. Pharmaceuticalmachinery.in; Shree Bhagwati Pharma Machinery Company, an ISO 9001:2000 company. http://www.pharmaceuticalmachinery.in/pharmaceutical_processing_machineries.htm#tray_dryer_pharmaceutical_machine. Accessed on 16-08-2017.

2. Pharm Technology Index, A Technological Platform and market Place; http://www.pharmatechnologyindex.com/Category/tray-dryer. Accessed on 29-11-2017.

3. Guidance for Industry Quality Systems Approach to Pharmaceutical CGMP Regulations; https://www.fda.gov/downloads/Drugs/Guidances/UCM070337.pdf. Accessed on 16-08-2017.

4. Suhaimi M. Review on the application of a tray dryer system for agricultural products. World applied sciences journal. 2013 May 12;22(3):424-33.

5. Jatto E, Okhamafe AO. An Overview of Pharmaceutical Validation and Process Controls in Drug Development. Tropical Journal of Pharmaceutical Research. 2002;1(2):115-22.

6. urswriter.com; Defining Requirements for Process Automation; http://www.urswriter.com/index.html?UserRequirements. Accessed on 16-08-2017.

7. McDowall R. Validation of chromatography data systems. Royal Society of Chemistry; 2016 Nov 23. 303-318.

8. theprojectdefinition.com; https://www.theprojectdefinition.com/?s=Factory+acceptance+test. Accessed on 19-08-2017.

9. theprojectdefinition.com; https://www.theprojectdefinition.com/?s=Site+acceptance+test. Accessed on 16-08-2017.

10. ofnisystems.com; Ofni Systems; http://www.ofnisystems.com/services/validation/. Accessed on 17-08-2017.

11. Chaloner-Larsson, Gillian, Roger Anderson, Anik Egan, Manoel Antonio Da Fonseca Costa Filho, Jorge F. Gomez Herrera, and World Health Organization. (1999) "A WHO guide to good manufacturing practice (GMP) requirements." Part 2: Validation, pp 36-52.

Received on 07.01.2019 Modified on 15.01.2019

Research J. Pharm. and Tech 2019; 12(2):805-811.

DOI: 10.5958/0974-360X.2019.00140.9