| Comment Record|
Mr. John Cooper ||
2002-04-22 10:23:14 |
Biocomposites Ltd |
| Comments for FDA General |
1. General Comments
Comments pertaining to Draft Guidance Document
21 CFR Part 888
Docket No: 01N-0411
Orthopaedic Devices: Proposed Classification for the Resorbable Calcium Salt Bone Void Filler Device.
To whom it may concern:
The product code as cited under Scope is incorrect. It is cited as MVQ but should be MQV.
2. Voluntary Consensus Standards
This section should include:-
c. ASTM F1088-87 “Standard Specification for Composition of Beta Tricalcium Phosphate for Surgical Implantation.”
d. ASTM F1581-99 “Standard Specification for Composition of Anorganic Bone for Surgical Implants.”
There is also a “Standard Specification for High Purity Calcium Sulfate Hemihydrate or Dihydrate for Surgical Implants” in preparation by ASTM and this should be included once approved.
3. Material Characterisation – Calcium Salt
a. Chemical Composition
This section should include:-
(5) Trace elements. The level of heavy metals including lead should be determined by Atomic Absorption Spectroscopy (AAS) or Inductively Coupled Plasma (ICP) and conform to the following limits:
Metal ppm max
The maximum allowable limit of all heavy metals determined as lead will be 50ppm.
4. Material Characterisation – Biological Source Material
a. For a calcium salt or calcium salt additive derived from a biological source or a calcium salt combined with a biological source material e.g., either animal or human tissue, firm assurance that the implant material has been appropriately sourced, adequately processed (i.e., for inactivation of viruses, bacteria, and fungi), and immunologically inactivated should be provided.
NB In the light of the potential consequences to a recipient of inappropriately sourced and/or inadequately processed biological source implant material we believe that “reasonable assurance” is not good enough.
5. Performance Testing
b. Animal testing…….
The time required for “complete resorption” of the device material can extend to many years for some currently approved implant materials including various hydroxyapatite ceramics. This would be impractical, if not impossible, to determine using an animal model. It may be better to reword this paragraph as follows:-
Animal testing to evaluate new bone formation and device resorption over the time required for biological healing may be necessary. Radiographic and histomorphometric analysis should be used to evaluate bone formation and device resorption. Histological analysis can be used to assess general biocompatibility and osteoconductive potential of the device implant material.
We believe that biomechanical testing to characterise the strength of the newly formed bone is inappropriate since there are no standard test procedures. Any strength results obtained would be so variable and dependent upon the testing protocols used as to be meaningless. For instance what animal model, defect site, defect size, defect shape/geometry, time of sacrifice, type of loading (e.g., torsion, three-point bend, four-point bend or tensile testing), plane of loading, rate of loading, control site (none, unfilled defect, autograft filled defect, predicate device filled defect) etc.,would be recommended? How many animals would need to be sacrificed in order to establish significance, and what would be the criteria for significance?
John J Cooper
Technical Research Director
for Biocomposites Ltd
Stoke on Trent